Is CAP2 p.Met53Ile (c.159G>A) pathogenic?

CAP2 p.Met53Ile (c.159G>A) is classified Uncertain significance in CAP2 (ClinVar, Single submitter, 1 submitter; last evaluated 2024-02-17). AlphaMissense: likely benign (0.2329); Rare (popmax 0.12%, eas).

How common is CAP2 p.Met53Ile (c.159G>A) in the general population?

CAP2 p.Met53Ile (c.159G>A) is rare (popmax 0.12%, eas) (gnomAD).

What do computational predictors say about CAP2 p.Met53Ile (c.159G>A)?

AlphaMissense predicts likely benign (score 0.2329) — an in-silico prediction, not a clinical call.

CAP2 p.Met53Ile

c.159G>A · rs200233388 · VCV3137005

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.2329 · ACMG-weighted

gnomAD v4.1

Rare

rare (popmax 0.12%, eas)

Missense predictors

0/3 damaging

AlphaMissense, REVEL, SaProt

Computational evidence

Protein change
AlphaMissense	0.2329	likely benign
REVEL	0.028	moderately benign-leaning
SaProt	LLR -5.18	tolerated
⇒ AlphaMissense, REVEL and SaProt all call this tolerated.
Splicing
SpliceAI	Δ0.21	acceptor loss, 37 bp away · masked 0 · deltas
Constraint at this position
Conservation	phyloP 5.1	GERP -0.57, phastCons 1
Overall
CADD	17.48	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 0.12% East Asian · 54/44,882 alleles

Filtering AF 0.0946% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.0855%

Overall 0.00366% 59/1,614,022 alleles · rare

Ancestry group	Frequency	1 in
East Asiangrpmax	0.12%	831
Remaining individualsnot grpmax-eligible	0.0032%	31,250
European (non-Finnish)	0.000254%	393,320

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.Met53Ile
Coding: c.159G>A
MANE Select: NM_019894 · reported on NM_006366
dbSNP: rs200233388
Type: single nucleotide variant
Location: chr6:17426627 (GRCh38)
Structure: AlphaFold pLDDT 88.01

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-met53ile (accessed [today's date]).

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