# NM_006137.7(CD7):c.308G>A (p.Arg103His)

https://sugi.bio/variant/cd7-p-arg103his

## Summary

**CD7 p.Arg103His (c.308G>A)** is classified **Likely benign** in CD7 (ClinVar, Single submitter, 1 submitter; last evaluated 2023-06-05). AlphaMissense: likely benign (0.0715); Ultra-rare (popmax 0.0329%, mid).

**At a glance:** Likely benign · review: Single submitter · rsID rs781698663 · 1 submitter · AlphaMissense likely benign · ultra-rare (popmax 0.0329%, mid)

## For patients & families {#patients}

This is a change in the CD7 gene that is classified as likely benign — not considered disease-causing, submitted by 1 submitter.

*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:** [Find a genetic counselor (NSGC)](https://findageneticcounselor.nsgc.org/).

## Identity {#identity}

| Field | Value |
| --- | --- |
| Gene | [CD7](https://sugi.bio/atlas/gene/CD7/) |
| Protein change (HGVS p.) | p.Arg103His |
| Coding change (HGVS c.) | c.308G>A |
| MANE Select transcript | [NM_006137](https://www.ncbi.nlm.nih.gov/nuccore/NM_006137) |
| dbSNP | [rs781698663](https://www.ncbi.nlm.nih.gov/snp/rs781698663/) |
| Variant type | single nucleotide variant |
| Location | chr17:82316756-82316756 (GRCh38) |
| ClinVar | [VCV2516851](https://www.ncbi.nlm.nih.gov/clinvar/variation/2516851/) |

**All HGVS expressions:** `NC_000017.10:g.80274632C>T`, `NC_000017.11:g.82316756C>T`, `NM_006137.7:c.308G>A`

## Computational & population evidence {#evidence}

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

- AlphaMissense **likely benign** (0.0715)
- REVEL 0.059 (moderately benign-leaning) — agrees with AlphaMissense
- SaProt LLR -6.795 (tolerated) — agrees with AlphaMissense
- → **In-silico consensus:** AlphaMissense, REVEL and SaProt all call this tolerated
- Conservation: phyloP -7.068, GERP -3.17 — fast-evolving / accelerated position
- CADD: **PHRED 0.002**. 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.*
- Regional missense constraint: **o/e 0.89** across the covering region of the MANE Select transcript (82,315,324–82,317,495), spanning 2,171 bp. Chi-square p 0.046. Describes the region, not this allele; gnomAD v4.1.1's own constrained determination. *Descriptive; no ACMG code applied.*
- SpliceAI: **below the reporting threshold**. This position is scored for a different substitution (C>G, Δ0.33 acceptor 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 (gnomAD v4.1): grpmax **0.0329%** (mid) · FAF95 0.0058% · FAF99 0.00241% · 2/6,084 in the highest group · 21/1,613,642 alleles overall — ultra-rare (popmax 0.0329%, mid).

| Ancestry group | Allele frequency | 1 in |
| --- | --- | --- |
| Middle Eastern (grpmax) | 0.0329% | 3,042 |
| South Asian | 0.00439% | 22,770 |
| Remaining individuals (not grpmax-eligible) | 0.0032% | 31,238 |
| Admixed American | 0.00167% | 59,990 |
| African / African-American | 0.00134% | 74,900 |
| European (non-Finnish) | 0.000932% | 107,269 |

*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}

**CD7** population constraint: LOEUF 1.673, pLI 2.1348e-08, missense-Z 0.089087. *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 **103** lies in a disulfide bond; the ig-like domain.

AlphaFold model confidence (whole protein): pLDDT 77.51, 44% of residues very-high.

**2 experimental structure(s)** (PDB): [12HP](https://www.rcsb.org/structure/12HP), [12NP](https://www.rcsb.org/structure/12NP).

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

*Describes the biological roles of CD7 (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:** CD7's established molecular role includes transmembrane signaling receptor activity. p.Arg103His falls in the ig-like domain.


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

**Molecular function:** transmembrane signaling receptor activity.

**Biological process:** positive regulation of T cell cytokine production.

## Clinical significance {#significance}

**Likely benign** — review status Single submitter *(criteria provided, single submitter)*, last evaluated 2023-06-05.

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

### Submitter classifications {#submitters}

| Submitter | Classification | Review | Method | Date |
| --- | --- | --- | --- | --- |
| Ambry Genetics | Likely benign | criteria provided, single submitter | clinical testing | 2023-06-05 |

**Reported phenotype names (ClinVar):** not specified, AllHighlyPenetrant.

## Similar variants {#similar}

Related CD7 variant pages (same residue, condition, or type): [CD7 p.Ala145Thr](/variant/cd7-p-ala145thr), [CD7 p.Ala154Asp](/variant/cd7-p-ala154asp), [CD7 p.Ala154Thr](/variant/cd7-p-ala154thr), [CD7 p.Ala15Val](/variant/cd7-p-ala15val), [CD7 p.Ala17Ser](/variant/cd7-p-ala17ser), [CD7 p.Ala184Val](/variant/cd7-p-ala184val), [CD7 p.Ala217Thr](/variant/cd7-p-ala217thr), [CD7 p.Ala218Thr](/variant/cd7-p-ala218thr).

### Data sources & attribution {#sources}

ClinVar (NCBI — public domain, built 2026-10-11); 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 2516851). 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.*