Is CAP2 p.Cys430fs (c.1288del) pathogenic?

CAP2 p.Cys430fs (c.1288del) is classified Pathogenic in CAP2 (ClinVar, No assertion criteria, 1 submitter; last evaluated 2023-08-03). Very rare (popmax 0.000934%, nfe); Associated with cardiomyopathy, dilated, 2I.

What condition is associated with CAP2 p.Cys430fs (c.1288del)?

CAP2 p.Cys430fs (c.1288del) is associated with cardiomyopathy, dilated, 2I (ClinVar).

How common is CAP2 p.Cys430fs (c.1288del) in the general population?

CAP2 p.Cys430fs (c.1288del) is very rare (popmax 0.000934%, nfe) (gnomAD).

CAP2 p.Cys430fs

c.1288del · rs781025932 · VCV2574651

Pathogenic No assertion criteria

Classification

Pathogenic

ClinVar

Review

No assertion criteria ☆☆☆☆

ClinVar · 1 submitter

Consequence

frameshift

predicted LoF

gnomAD v4.1

Rare

very rare (popmax 0.000934%, nfe)

Conditions

cardiomyopathy, dilated, 2I

Computational evidence

Protein change
Missense predictors do not apply to this variant type; conservation carries the signal.
Consequence	frameshift	predicted loss-of-function; NMD-escape possible for C-terminal truncations
Splicing
SpliceAI	—	not assessed · substitutions only
Constraint at this position
Conservation	phyloP 0.086	GERP -0.3, phastCons 0.91
Overall
CADD	33.0	PHRED · no single calibrated threshold — expert panels disagree

Predicted loss-of-function is descriptive, not an applied PVS1 code.

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.000934% European (non-Finnish) · 11/1,177,650 alleles

Filtering AF 0.000501% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.000366%

Overall 0.000683% 11/1,611,206 alleles · very rare

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.Cys430fs
Coding: c.1288del
MANE Select: NM_019894 · reported on NM_006366
dbSNP: rs781025932
Type: Deletion
Location: chr6:17551542 (GRCh38)
Structure: AlphaFold pLDDT 88.01
Residue 430: the peptidase s1 domain

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.Ser291fs Likely pathogenic ★ same condition
CAP2 p.Arg17His Uncertain significance ★★ ⚠ same condition
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

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-cys430fs (accessed [today's date]).

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