Is CAP2 p.Ala162Thr (c.484G>A) pathogenic?

CAP2 p.Ala162Thr (c.484G>A) is classified Uncertain significance in CAP2 (ClinVar, Single submitter, 1 submitter; last evaluated 2022-11-18). AlphaMissense: likely pathogenic (0.7365); Very rare (popmax 0.00334%, amr).

How common is CAP2 p.Ala162Thr (c.484G>A) in the general population?

CAP2 p.Ala162Thr (c.484G>A) is very rare (popmax 0.00334%, amr) (gnomAD).

What do computational predictors say about CAP2 p.Ala162Thr (c.484G>A)?

AlphaMissense predicts likely pathogenic (score 0.7365) — an in-silico prediction, not a clinical call.

CAP2 p.Ala162Thr

c.484G>A · rs778806530 · VCV3137006

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely pathogenic

0.7365 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 0.00334%, amr)

Missense predictors

2/2 damaging

AlphaMissense, SaProt · REVEL no call

Computational evidence

Protein change
AlphaMissense	0.7365	likely pathogenic · top 9% in CAP2
REVEL	0.518	indeterminate
SaProt	LLR -11.54	damaging
⇒ AlphaMissense and SaProt both call this damaging; REVEL makes no call.
Splicing
SpliceAI	Δ0.25	acceptor loss, 39 bp away · masked 0 · deltas
Constraint at this position
Conservation	phyloP 12	GERP 1.9, phastCons 1
Overall
CADD	28.6	PHRED · no single calibrated threshold — expert panels disagree

ClinVar classifies this uncertain; the computational predictors unanimously lean damaging — 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 0.00334% Admixed American · 2/59,952 alleles

Filtering AF 0.000553% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.000207%

Overall 0.000685% 10/1,459,240 alleles · very rare

Ancestry group	Frequency	1 in
Admixed Americangrpmax	0.00334%	29,976
South Asian	0.0022%	45,491
Remaining individualsnot grpmax-eligible	0.0016%	62,406
European (non-Finnish)	0.000425%	235,551

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.Ala162Thr
Coding: c.484G>A
MANE Select: NM_019894 · reported on NM_006366
dbSNP: rs778806530
Type: single nucleotide variant
Location: chr6:17507680 (GRCh38)
Structure: AlphaFold pLDDT 88.01
Residue 162: a disulfide bond; 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.Ala262Pro Uncertain significance ★ ⚠ same type
CAP2 p.Ala272Thr Uncertain significance ★ ⚠ same type
CAP2 p.Ala294Thr Uncertain significance ★ ⚠ same type
CAP2 p.Ala435Thr 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-ala162thr (accessed [today's date]).

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