# NM_005898.5(CAPRIN1):c.879G>A (p.Glu293=)

https://sugi.bio/variant/caprin1-p-glu293

## Summary

**CAPRIN1 p.Glu293= (c.879G>A)** is classified **Pathogenic** in CAPRIN1 (ClinVar, No assertion criteria, 1 submitter; last evaluated 2024-04-11). No allele count reported in gnomAD v4.1 (AN 1,613,696); Associated with neurodevelopmental disorder with language impairment, autism, and attention deficit-hyperactivity disorder.

**At a glance:** Pathogenic · review: No assertion criteria · rsID rs2496067678 · 1 submitter · 1 linked condition · no allele count reported in gnomAD v4.1 (AN 1,613,696)

## For patients & families {#patients}

This is a change in the CAPRIN1 gene that is reported as disease-causing, but on limited review, submitted by 1 submitter, and is linked to neurodevelopmental disorder with language impairment, autism, and attention deficit-hyperactivity disorder.

*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.*

**Support & next steps:** [Condition overview & support (NIH GARD)](https://rarediseases.info.nih.gov/diseases/0028082/index) · [Find a genetic counselor (NSGC)](https://findageneticcounselor.nsgc.org/).

## Identity {#identity}

| Field | Value |
| --- | --- |
| Gene | [CAPRIN1](https://sugi.bio/atlas/gene/CAPRIN1/) |
| Protein change (HGVS p.) | p.Glu293= |
| Coding change (HGVS c.) | c.879G>A |
| MANE Select transcript | [NM_005898](https://www.ncbi.nlm.nih.gov/nuccore/NM_005898) |
| dbSNP | [rs2496067678](https://www.ncbi.nlm.nih.gov/snp/rs2496067678/) |
| Variant type | single nucleotide variant |
| Location | chr11:34082877-34082877 (GRCh38) |
| ClinVar | [VCV3069139](https://www.ncbi.nlm.nih.gov/clinvar/variation/3069139/) |

**All HGVS expressions:** `NC_000011.10:g.34082877G>A`, `NC_000011.9:g.34104424G>A`, `NM_005898.5:c.879G>A`, `NM_203364.3:c.879G>A`

## Computational & population evidence {#evidence}

**Concordance:** 1 independent predictor **concordant** with the ClinVar classification.

- **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 and, for splice-region changes, SpliceAI (below), not from a missing predictor score.
- SpliceAI predicts **donor loss** (Δ 0.39) — consistent with the pathogenic call
- Conservation: phyloP 11.832, GERP 1.66, phastCons 1 — highly conserved position (PP3-type support)
- CADD: **PHRED 22.7**. 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 deltas (raw): acceptor loss **0.00**, donor loss **0.39**, acceptor gain **0.00**, donor gain **0.01**. Largest is donor loss.
- SpliceAI deltas (masked): acceptor loss **0.00**, donor loss **0.39**, acceptor gain **0.00**, donor gain **0.01**.
- Pangolin: Δ**0.72** (loss), gain 0.01 / loss 0.72. Agrees with SpliceAI. An independent predictor to SpliceAI — a different model trained on different data. *Descriptive; ClinGen's SVI calibration covers SpliceAI, not Pangolin, so no ACMG code is assigned.*
- Population frequency: **no allele count reported in gnomAD v4.1 (AN 1,613,696)** — rarity (ACMG PM2) and BA1/BS1 cannot be assessed for this variant.

*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}

**CAPRIN1** population constraint: LOEUF 0.372, pLI 1, missense-Z 1.2679; 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.*

Curated gene–disease validity (ClinGen):

- **neurodegeneration, childhood-onset, with cerebellar ataxia and cognitive decline** — Moderate (AD)
- **neurodevelopmental disorder with language impairment, autism, and attention deficit-hyperactivity disorder** — Moderate (AD)

## Protein context {#protein}


AlphaFold model confidence (whole protein): pLDDT 58.64, 29% of residues very-high.

**6 experimental structure(s)** (PDB): [4WBE](https://www.rcsb.org/structure/4WBE), [4WBP](https://www.rcsb.org/structure/4WBP), [6TA7](https://www.rcsb.org/structure/6TA7), [7XHG](https://www.rcsb.org/structure/7XHG), [8TH7](https://www.rcsb.org/structure/8TH7), [9HFU](https://www.rcsb.org/structure/9HFU).

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

*Describes the biological roles of CAPRIN1 (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:** CAPRIN1's established molecular role includes RNA binding.


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

**Molecular function:** RNA binding, mRNA binding, ATP binding, signaling adaptor activity, molecular function activator activity, molecular condensate scaffold activity.

**Biological process:** negative regulation of translation, positive regulation of cytoplasmic stress granule assembly, regulation of deadenylation-dependent decapping of nuclear-transcribed mRNA, membraneless organelle assembly.

## Clinical significance {#significance}

**Pathogenic** — review status No assertion criteria *(no assertion criteria provided)*, last evaluated 2024-04-11.

**Submitter consensus:** unanimous (1/1 Pathogenic).

### Submitter classifications {#submitters}

| Submitter | Classification | Review | Method | Date |
| --- | --- | --- | --- | --- |
| OMIM | Pathogenic | no assertion criteria provided | literature only | 2024-04-11 |

## Associated conditions {#conditions}

[neurodevelopmental disorder with language impairment, autism, and attention deficit-hyperactivity disorder](https://sugi.bio/atlas/disease/neurodevelopmental-disorder-with-language-impairment-autism-and-attention-deficit-hyperactivity-disorder/).

**Reported phenotype names (ClinVar):** Neurodevelopmental disorder with language impairment, autism, and attention deficit-hyperactivity disorder.

## Same-residue context {#hotspot}

Residue **293** carries **1 other pathogenic ClinVar variant** — a recurrently-mutated position: [CAPRIN1 p.Glu293fs](/variant/caprin1-p-glu293fs). *Positional co-occurrence of independent ClinVar records, not functional proof.*

## Similar variants {#similar}

Related CAPRIN1 variant pages (same residue, condition, or type): [CAPRIN1 p.Arg458Ter](/variant/caprin1-p-arg458ter), [CAPRIN1 p.Arg356Ter](/variant/caprin1-p-arg356ter), [CAPRIN1 p.Arg358Ter](/variant/caprin1-p-arg358ter), [CAPRIN1 p.Glu293fs](/variant/caprin1-p-glu293fs), [CAPRIN1 p.Gly31Ter](/variant/caprin1-p-gly31ter), [CAPRIN1 p.Ser482Ter](/variant/caprin1-p-ser482ter), [CAPRIN1 c.826+16A>G](/variant/caprin1-c-826-plus-16a-g), [CAPRIN1 p.Gln298Ter](/variant/caprin1-p-gln298ter).

### 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 3069139). 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.*