Is CAP2 p.Met1Thr (c.2T>C) pathogenic?

CAP2 p.Met1Thr (c.2T>C) is classified Uncertain significance in CAP2 (ClinVar, Single submitter, 1 submitter; last evaluated 2021-11-07). Very rare (popmax 0.000763%, nfe); Associated with cardiomyopathy, dilated, 2I.

What condition is associated with CAP2 p.Met1Thr (c.2T>C)?

CAP2 p.Met1Thr (c.2T>C) is associated with cardiomyopathy, dilated, 2I (ClinVar).

How common is CAP2 p.Met1Thr (c.2T>C) in the general population?

CAP2 p.Met1Thr (c.2T>C) is very rare (popmax 0.000763%, nfe) (gnomAD).

CAP2 p.Met1Thr

c.2T>C · rs781551693 · VCV2688715

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

Consequence

start-loss

predicted LoF

gnomAD v4.1

Rare

very rare (popmax 0.000763%, nfe)

Conditions

cardiomyopathy, dilated, 2I

Computational evidence

Protein change
Missense predictors do not apply to this variant type; conservation carries the signal.
Consequence	start-loss	predicted loss-of-function
REVEL	0.31	indeterminate
Splicing
SpliceAI	<0.2	all four deltas below 0.2 · T>G here scores Δ0.22 · evaluated, not missing
Constraint at this position
Conservation	phyloP 6.2	GERP 2.4, phastCons 1
Overall
CADD	22.9	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 0.000763% European (non-Finnish) · 9/1,180,038 alleles

Filtering AF 0.000359% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.00026%

Overall 0.000867% 14/1,614,062 alleles · very rare

Ancestry group	Frequency	1 in
Remaining individualsnot grpmax-eligible	0.008%	12,496
European (non-Finnish)grpmax	0.000763%	131,115

Remaining individuals shows a higher raw frequency than the grpmax group above it. gnomAD excludes bottlenecked groups — Finnish, Ashkenazi Jewish, Amish and “Remaining individuals” — from grpmax, because founder effects make their frequencies unrepresentative for filtering. The table is sorted by frequency, so an excluded group can sit above the grpmax row.

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.Met1Thr
Coding: c.2T>C
MANE Select: NM_019894 · reported on NM_006366
dbSNP: rs781551693
Type: single nucleotide variant
Location: chr6:17421557 (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.Arg17His Uncertain significance ★★ ⚠ same condition
CAP2 p.Arg13Gln 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
TMPRSS4 p.Ala44Val Likely benign ★★ 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-met1thr (accessed [today's date]).

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