Is CAP2 p.Val103Met (c.307G>A) pathogenic?

CAP2 p.Val103Met (c.307G>A) is classified Uncertain significance in CAP2 (ClinVar, Single submitter, 1 submitter; last evaluated 2024-08-10). AlphaMissense: likely benign (0.078); Ultra-rare (popmax 0.0253%, sas).

How common is CAP2 p.Val103Met (c.307G>A) in the general population?

CAP2 p.Val103Met (c.307G>A) is ultra-rare (popmax 0.0253%, sas) (gnomAD).

What do computational predictors say about CAP2 p.Val103Met (c.307G>A)?

AlphaMissense predicts likely benign (score 0.078) — an in-silico prediction, not a clinical call.

CAP2 p.Val103Met

c.307G>A · VCV3484688

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.078 · ACMG-weighted

gnomAD v4.1

Rare

ultra-rare (popmax 0.0253%, sas)

Missense predictors

0/3 damaging

AlphaMissense, REVEL, SaProt

Computational evidence

Protein change
AlphaMissense	0.078	likely benign
REVEL	0.101	moderately benign-leaning
SaProt	LLR -2.22	tolerated
⇒ AlphaMissense, REVEL and SaProt all call this tolerated.
Splicing
SpliceAI	Δ0.25	acceptor loss, 6 bp away · masked 0 · deltas
Constraint at this position
Conservation	phyloP 5	GERP 0.68, phastCons 1
Overall
CADD	21.9	PHRED · no single calibrated threshold — expert panels disagree

ClinVar classifies this uncertain; the computational predictors unanimously lean tolerated — a triage signal, not a reclassification

AlphaMissense carries the ACMG weight for missense; REVEL and SaProt are independent agreement signals.

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.0253% South Asian · 23/91,086 alleles

Filtering AF 0.0172% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.0146%

Overall 0.00235% 38/1,614,172 alleles · ultra-rare

Ancestry group	Frequency	1 in
South Asiangrpmax	0.0253%	3,960
Remaining individualsnot grpmax-eligible	0.0112%	8,930
East Asian	0.00891%	11,222
Ashkenazi Jewishnot grpmax-eligible	0.00338%	29,606
European (non-Finnish)	0.000254%	393,340

Rarity supports pathogenicity (ACMG PM2); frequency above a disease-specific BA1/BS1 threshold argues against it. A variant frequent in one ancestry group can be near-absent in others, so a single global figure can mislead.

Variant & gene context

Gene: CAP2
Protein: p.Val103Met
Coding: c.307G>A
MANE Select: NM_019894 · reported on NM_006366
Type: single nucleotide variant
Location: chr6:17507175 (GRCh38)
Structure: AlphaFold pLDDT 88.01
Residue 103: the srcr domain

Full CAP2 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Similar variants

CAP2 p.Arg17His Uncertain significance ★★ ⚠ same type
CAP2 p.His203Arg Uncertain significance ★★ ⚠ same type
TMPRSS4 p.Ala44Val Likely benign ★★ same type
CAP2 c.1003-5T>G Uncertain significance ★ same type
CAP2 p.Ala162Thr Uncertain significance ★ ⚠ same type
CAP2 p.Ala262Pro Uncertain significance ★ ⚠ same type
CAP2 p.Ala272Thr Uncertain significance ★ ⚠ same type
CAP2 p.Ala294Thr Uncertain significance ★ ⚠ same type

Built on 18 open, versioned datasets — ClinVar, gnomAD, AlphaMissense, REVEL, ClinGen & more — plus Sugi Variant's own cross-source analysis. Source data 2026-01–2026-10, ClinVar 2026-10. Full sources & versions →

Cite Sugi Variant

Gür T. Sugi Variant: A Deterministic Per-Variant Germline Reference from a Knowledge Graph for Humans and AI Agents. 2026. doi:10.5281/zenodo.21509445. This variant: https://sugi.bio/variant/cap2-p-val103met (accessed [today's date]).

Preprint & method: sugi.bio/variant/method Machine-readable: this page as Markdown