# NM_001011.4(RPS7):c.261C>T (p.Phe87=)

https://sugi.bio/variant/rps7-p-phe87

## Summary

**RPS7 p.Phe87= (c.261C>T)** is classified **Likely benign** in RPS7 (ClinVar, Single submitter, 1 submitter; last evaluated 2022-12-15). Absent from gnomAD v4.1; Associated with Diamond-Blackfan anemia 8.

**At a glance:** Likely benign · review: Single submitter · rsID rs760461885 · 1 submitter · 1 linked condition · absent from gnomAD v4.1

## For patients & families {#patients}

This is a change in the RPS7 gene that is classified as likely benign — not considered disease-causing, submitted by 1 submitter, and is linked to Diamond-Blackfan anemia 8.

*Reference information, not medical advice, and not a prediction for any individual. A genetic counselor or clinician can interpret what it means for you and your family.*

|  |  |
| --- | --- |
| Typical inheritance (of this condition) | Autosomal dominant |
| Age of onset (of this condition) | Childhood, Infancy, Neonatal |
| Prevalence | 1-9 / 1 000 000 (Europe) |
| Diagnostic panels | RPS7 is a diagnostic-grade gene on 9 Genomics England panels |

**Commonly reported features of Diamond-Blackfan anemia** (across patients with this condition; presentation varies — frequencies from Orphanet):

- Pure red cell aplasia — Very frequent (99-80%)
- Elevated red cell adenosine deaminase activity — Very frequent (99-80%)
- Abnormality of the head — Frequent (79-30%)
- Pallor — Frequent (79-30%)
- Lethargy — Frequent (79-30%)
- Growth delay — Frequent (79-30%)
- Small for gestational age — Frequent (79-30%)
- Reticulocytopenia — Frequent (79-30%)

**Support & next steps:** [Condition overview & support (NIH GARD)](https://rarediseases.info.nih.gov/diseases/0015570/index) · [Find a genetic counselor (NSGC)](https://findageneticcounselor.nsgc.org/).

## Identity {#identity}

| Field | Value |
| --- | --- |
| Gene | [RPS7](https://sugi.bio/atlas/gene/RPS7/) |
| Protein change (HGVS p.) | p.Phe87= |
| Coding change (HGVS c.) | c.261C>T |
| MANE Select transcript | [NM_001011](https://www.ncbi.nlm.nih.gov/nuccore/NM_001011) |
| dbSNP | [rs760461885](https://www.ncbi.nlm.nih.gov/snp/rs760461885/) |
| Variant type | single nucleotide variant |
| Location | chr2:3576600-3576600 (GRCh38) |
| ClinVar | [VCV2965029](https://www.ncbi.nlm.nih.gov/clinvar/variation/2965029/) |

**All HGVS expressions:** `LRG_1148:g.6338C>T`, `LRG_1148t1:c.261C>T`, `NC_000002.11:g.3624190C>T`, `NC_000002.12:g.3576600C>T`, `NG_011744.1:g.6338C>T`, `NM_001011.4:c.261C>T`

## Computational & population evidence {#evidence}

**Concordance:** Mixed / partial computational evidence (see below).

- **Missense predictors (AlphaMissense/REVEL/SaProt) do not apply** to this variant type — they score amino-acid substitutions only. For non-missense variants the computational signal comes from conservation (below), not from a missing predictor score.
- Conservation: phyloP 0.968, GERP -1.28, phastCons 1 — weakly conserved position
- CADD: **PHRED 14.95**. No single ClinGen-calibrated threshold exists and the expert panels that use CADD disagree — GUCY2D/AIPL1 require ≥ 20.0 for an untranslated-region variant, ABCA4 ≥ 28.1 for a synonymous or indel variant, the Pulmonary Hypertension panel imports Pejaver 2022's missense-calibrated numbers, and the Antibody Deficiencies panel declines CADD entirely for PIK3CD. CADD v1.7 also incorporates Zoonomia phyloP, so it partly re-expresses the conservation above. *Descriptive; no threshold applied.*
- SpliceAI: **below the reporting threshold**. This position is scored for a different substitution (C>A, Δ0.41 donor gain), so this allele was evaluated and its deltas all fell under Δ0.2 — a prediction of no splicing effect for this allele, not a gap in our data. *No ACMG code assigned.*
- Population frequency: **absent from gnomAD v4.1** — a rarity signal (ACMG PM2-supporting), not evidence of pathogenicity on its own.

*Computational predictors are not independent (ClinGen Variant Classification guidance): AlphaMissense (Cheng et al. 2023) carries the ACMG weight for missense and conservation (phyloP/GERP/phastCons) for non-missense; REVEL (Pejaver-2022 calibrated strength bands) and SaProt (Su et al. 2023, structure-aware, ClinVar-independent protein language model, raw LLR) are shown as orthogonal agreement signals, not additive. For frequency, the gnomAD v4.1 grpmax filtering allele frequency (FAF95) is ClinGen's designated BA1/BS1 input (gnomAD v4 guidance v3.0, June 2025); BA1/BS1 thresholds are disease-specific, not a blanket 5%. Predictions, not a clinical determination.*

## Gene constraint & dosage {#gene-context}

**RPS7** population constraint: LOEUF 0.317, pLI 0.99613, missense-Z 1.8932; ClinGen dosage — haploinsufficiency 2, triplosensitivity 0 (0–3 scale). *Lower LOEUF and higher pLI indicate a gene that tolerates loss-of-function poorly; ClinGen dosage is the curated haploinsufficiency call.*

## Protein context {#protein}

Residue **87** lies in a turn.

AlphaFold model confidence (whole protein): pLDDT 87.04, 56% of residues very-high.

**182 experimental structure(s)** (PDB): [4UG0](https://www.rcsb.org/structure/4UG0), [4V6X](https://www.rcsb.org/structure/4V6X), [5A2Q](https://www.rcsb.org/structure/5A2Q), [5AJ0](https://www.rcsb.org/structure/5AJ0), [5FLX](https://www.rcsb.org/structure/5FLX), [5LKS](https://www.rcsb.org/structure/5LKS) — incl. mutant structure 28ZU.

## What this gene does {#gene-function}

*Describes the biological roles of RPS7 (the gene this variant disrupts) — not effects measured for this specific variant. A damaging variant is expected to affect these functions and pathways; the degree depends on the variant.*

**How this variant is thought to act:** RPS7's established molecular role includes RNA binding. In Reactome, RPS7 is annotated in disease pathway(s) including **SARS-CoV-1 modulates host translation machinery**, **SARS-CoV-2 modulates host translation machinery**.

**Disease mechanism (Reactome):** RPS7 loss or alteration is curated in [SARS-CoV-1 modulates host translation machinery](https://reactome.org/content/detail/R-HSA-9735869), [SARS-CoV-2 modulates host translation machinery](https://reactome.org/content/detail/R-HSA-9754678), [Viral mRNA Translation](https://reactome.org/content/detail/R-HSA-192823).

### Pathways affected {#pathways}

RPS7 participates in **22 Reactome pathways** (⚕ = disease pathway):

| Pathway (Reactome) | Evidence |
| --- | --- |
| ⚕ [SARS-CoV-1 modulates host translation machinery](https://reactome.org/content/detail/R-HSA-9735869) | curated |
| ⚕ [SARS-CoV-2 modulates host translation machinery](https://reactome.org/content/detail/R-HSA-9754678) | curated |
| ⚕ [Viral mRNA Translation](https://reactome.org/content/detail/R-HSA-192823) | curated |
| [Formation of a pool of free 40S subunits](https://reactome.org/content/detail/R-HSA-72689) | curated |
| [Formation of the ternary complex, and subsequently, the 43S complex](https://reactome.org/content/detail/R-HSA-72695) | curated |
| [GTP hydrolysis and joining of the 60S ribosomal subunit](https://reactome.org/content/detail/R-HSA-72706) | curated |
| [IFIT antiviral response](https://reactome.org/content/detail/R-HSA-9684482) | curated |
| [L13a-mediated translational silencing of Ceruloplasmin expression](https://reactome.org/content/detail/R-HSA-156827) | curated |
| [Major pathway of rRNA processing in the nucleolus and cytosol](https://reactome.org/content/detail/R-HSA-6791226) | curated |
| [Nonsense Mediated Decay (NMD) enhanced by the Exon Junction Complex (EJC)](https://reactome.org/content/detail/R-HSA-975957) | curated |
| [Nonsense Mediated Decay (NMD) independent of the Exon Junction Complex (EJC)](https://reactome.org/content/detail/R-HSA-975956) | curated |
| [PELO:HBS1L and ABCE1 dissociate a ribosome on a non-stop mRNA](https://reactome.org/content/detail/R-HSA-9954714) | curated |
| [Ribosomal scanning and start codon recognition](https://reactome.org/content/detail/R-HSA-72702) | curated |
| [Translation initiation complex formation](https://reactome.org/content/detail/R-HSA-72649) | curated |
| [ZNF598 and the Ribosome-associated Quality Trigger (RQT) complex dissociate a ribosome stalled on a no-go mRNA](https://reactome.org/content/detail/R-HSA-9954716) | curated |
| [Eukaryotic Translation Termination](https://reactome.org/content/detail/R-HSA-72764) | electronic |
| [Peptide chain elongation](https://reactome.org/content/detail/R-HSA-156902) | electronic |
| [Regulation of expression of SLITs and ROBOs](https://reactome.org/content/detail/R-HSA-9010553) | electronic |
| [Response of EIF2AK4 (GCN2) to amino acid deficiency](https://reactome.org/content/detail/R-HSA-9633012) | electronic |
| [SRP-dependent cotranslational protein targeting to membrane](https://reactome.org/content/detail/R-HSA-1799339) | electronic |
| [Selenocysteine synthesis](https://reactome.org/content/detail/R-HSA-2408557) | electronic |
| [rRNA modification in the nucleus and cytosol](https://reactome.org/content/detail/R-HSA-6790901) | electronic |

### Molecular function & processes (GO — experimentally supported) {#go}

**Molecular function:** RNA binding, mRNA 3'-UTR binding, structural constituent of ribosome, protein kinase binding, mRNA 5'-UTR binding, ubiquitin ligase inhibitor activity.

**Biological process:** rRNA processing, ribosomal small subunit biogenesis, positive regulation of intrinsic apoptotic signaling pathway by p53 class mediator, negative regulation of ubiquitin-dependent protein catabolic process.

## Clinical significance {#significance}

**Likely benign** — review status Single submitter *(criteria provided, single submitter)*, last evaluated 2022-12-15.

**Submitter consensus:** unanimous (1/1 Likely benign).

### Submitter classifications {#submitters}

| Submitter | Classification | Review | Method | Date |
| --- | --- | --- | --- | --- |
| Labcorp Genetics (formerly Invitae), Labcorp | Likely benign | criteria provided, single submitter | clinical testing | 2022-12-15 |

## Associated conditions {#conditions}

[Diamond-Blackfan anemia 8](https://sugi.bio/atlas/disease/diamond-blackfan-anemia-8/).

**Reported phenotype names (ClinVar):** Diamond-Blackfan anemia 8, RPS7-Related Diamond-Blackfan Anemia.

## Similar variants {#similar}

Related RPS7 variant pages (same residue, condition, or type): [RPS7 c.75+1G>A](/variant/rps7-c-75-plus-1g-a), [RPS7 c.356+6T>C](/variant/rps7-c-356-plus-6t-c), [RPS7 c.-27C>T](/variant/rps7-c-minus-27c-t), [RPS7 p.Ala26Val](/variant/rps7-p-ala26val), [RPS7 p.Ala38Val](/variant/rps7-p-ala38val), [RPS7 p.Arg145His](/variant/rps7-p-arg145his), [RPS7 p.Arg152Pro](/variant/rps7-p-arg152pro), [RPS7 p.Asn12Ser](/variant/rps7-p-asn12ser).

### Data sources & attribution {#sources}

ClinVar (NCBI — public domain, built 2026-10-14); gnomAD v4.1 (Broad Institute, built 2026-10-06); AlphaMissense (Cheng et al. 2023, © Google DeepMind — CC BY 4.0, built 2026-01-27); REVEL (Ioannidis et al. 2016 — ODbL, built 2026-07-13); SaProt (Su et al. 2023 — MIT, built 2026-07-14); SpliceAI (Illumina — free for non-commercial use, built 2026-10-13); CADD (Rentzsch et al. 2019, University of Washington — free for non-commercial use, built 2026-10-10); Conservation (phyloP/phastCons/GERP) (UCSC hg38 470-way mammal (Hiller Lab) + Ensembl Compara, built 2026-07-12); gnomAD Non-coding Constraint (Gnocchi) (Chen et al. 2024, Broad Institute — CC0, built 2026-10-11); gnomAD Regional Missense Constraint (Broad Institute — CC0, built 2026-10-13); Pangolin (Zeng & Li 2022 — CC BY 4.0, built 2026-10-11); Repeat regions (UCSC — RepeatMasker, TRF, segmental duplications, built 2026-10-11); ClinGen (ClinGen, built 2026-09-22); UniProt (CC BY 4.0); Reactome / GO (CC BY 4.0, built 2026-09-23); MaveDB (per-record license, built 2026-10-11); CIViC (CC0, built 2026-09-22); Orphanet (Orphanet, built 2026-06-12)

*Primary record: NCBI ClinVar (variation 2965029). Classifications reflect these databases as of the page's build date and may change. Free reference use — not medical advice; consult the primary submitters and a clinician.*