Is CAP2 p.Arg278Cys (c.832C>T) pathogenic?

CAP2 p.Arg278Cys (c.832C>T) is classified Uncertain significance in CAP2 (ClinVar, Single submitter, 1 submitter; last evaluated 2023-06-29). AlphaMissense: likely benign (0.2398); Very rare (popmax 0.0044%, sas).

How common is CAP2 p.Arg278Cys (c.832C>T) in the general population?

CAP2 p.Arg278Cys (c.832C>T) is very rare (popmax 0.0044%, sas) (gnomAD).

What do computational predictors say about CAP2 p.Arg278Cys (c.832C>T)?

AlphaMissense predicts likely benign (score 0.2398) — an in-silico prediction, not a clinical call.

CAP2 p.Arg278Cys

c.832C>T · rs771332228 · VCV2597569

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.2398 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 0.0044%, sas)

Missense predictors

0/2 damaging

AlphaMissense, SaProt · REVEL no call

Computational evidence

Protein change
AlphaMissense	0.2398	likely benign
REVEL	0.357	indeterminate
SaProt	LLR -6.45	tolerated
⇒ AlphaMissense and SaProt both call this tolerated; REVEL makes no call.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 4	GERP 1.1, phastCons 1
Overall
CADD	27.4	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 0.0044% South Asian · 4/91,010 alleles

Filtering AF 0.00143% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.000892%

Overall 0.0011% 16/1,461,130 alleles · very rare

Ancestry group	Frequency	1 in
South Asiangrpmax	0.0044%	22,753
Remaining individualsnot grpmax-eligible	0.0016%	62,472
European (non-Finnish)	0.000933%	107,236

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.Arg278Cys
Coding: c.832C>T
MANE Select: NM_019894 · reported on NM_006366
dbSNP: rs771332228
Type: single nucleotide variant
Location: chr6:17540978 (GRCh38)
Structure: AlphaFold pLDDT 88.01
Residue 278: a disulfide bond; the peptidase s1 domain

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

Similar variants

TMPRSS4 p.Ile278Val Likely benign ★ same residue
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

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-arg278cys (accessed [today's date]).

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