Is CAP2 p.Arg17His (c.50G>A) pathogenic?

CAP2 p.Arg17His (c.50G>A) is classified Uncertain significance in CAP2 (ClinVar, Multiple submitters, 2 submitters; last evaluated 2023-11-28). AlphaMissense: likely benign (0.1166); Very rare (popmax 0.00669%, eas); Associated with cardiomyopathy, dilated, 2I.

What condition is associated with CAP2 p.Arg17His (c.50G>A)?

CAP2 p.Arg17His (c.50G>A) is associated with cardiomyopathy, dilated, 2I (ClinVar).

How common is CAP2 p.Arg17His (c.50G>A) in the general population?

CAP2 p.Arg17His (c.50G>A) is very rare (popmax 0.00669%, eas) (gnomAD).

What do computational predictors say about CAP2 p.Arg17His (c.50G>A)?

AlphaMissense predicts likely benign (score 0.1166) — an in-silico prediction, not a clinical call.

CAP2 p.Arg17His

c.50G>A · rs141863829 · VCV3137007

Uncertain significance Multiple submitters

Classification

Uncertain significance

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 2 submitters

AlphaMissense

likely benign

0.1166 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 0.00669%, eas)

Missense predictors

1/2 damaging

AlphaMissense, SaProt · REVEL no call

Conditions

cardiomyopathy, dilated, 2I

Computational evidence

Protein change
AlphaMissense	0.1166	likely benign
REVEL	0.417	indeterminate
SaProt	LLR -12.74	damaging
⇒ SaProt calls this damaging; AlphaMissense does not; REVEL makes no call.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 9.8	GERP 2.4, phastCons 1
Overall
CADD	32.0	PHRED · no single calibrated threshold — expert panels disagree

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

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.00669% East Asian · 3/44,874 alleles

Filtering AF 0.00177% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.000891%

Overall 0.000682% 11/1,613,990 alleles · very rare

Ancestry group	Frequency	1 in
East Asiangrpmax	0.00669%	14,958
Admixed American	0.00333%	30,010
Remaining individualsnot grpmax-eligible	0.0016%	62,506
European (non-Finnish)	0.000424%	235,974

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.Arg17His
Coding: c.50G>A
MANE Select: NM_019894 · reported on NM_006366
dbSNP: rs141863829
Type: single nucleotide variant
Location: chr6:17421605 (GRCh38)
Structure: AlphaFold pLDDT 88.01

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

Disease context

cardiomyopathy, dilated, 2I — disease report on Sugi Atlas → Associated genes, phenotypes, clinical trials & treatments

Similar variants

CAP2 p.Arg17Leu Uncertain significance ★ ⚠ same residue
CAP2 p.Arg13Gln Uncertain significance ★ ⚠ same condition
CAP2 p.Met1Thr Uncertain significance ★ same condition
CAP2 c.636+1G>A Pathogenic same condition
CAP2 p.Tyr316Ter Pathogenic same condition
CAP2 p.Ser291fs Likely pathogenic ★ same condition
CAP2 p.Cys430fs Pathogenic same condition
CAP2 p.His203Arg 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-arg17his (accessed [today's date]).

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