Is CAPN14 p.Val401Met (c.1201G>A) pathogenic?

CAPN14 p.Val401Met (c.1201G>A) is classified Uncertain significance in CAPN14 (ClinVar, Single submitter, 1 submitter; last evaluated 2023-11-22). AlphaMissense: ambiguous (0.3758); Very rare (popmax 0.00244%, eas).

How common is CAPN14 p.Val401Met (c.1201G>A) in the general population?

CAPN14 p.Val401Met (c.1201G>A) is very rare (popmax 0.00244%, eas) (gnomAD).

What do computational predictors say about CAPN14 p.Val401Met (c.1201G>A)?

AlphaMissense predicts ambiguous (score 0.3758) — an in-silico prediction, not a clinical call.

CAPN14 p.Val401Met

c.1201G>A · rs1167740802 · VCV3137086

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

ambiguous

0.3758 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 0.00244%, eas)

Computational evidence

Protein change
AlphaMissense	0.3758	ambiguous
REVEL	0.456	indeterminate
SaProt	LLR -9.94	tolerated
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 0.76	GERP 0.61, phastCons 0.42
Regional constraint	o/e 1.01	unconstrained · MANE · 31 kb · p 0.76 · regional, not allelic
Overall
CADD	22.2	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 0.00244% East Asian · 1/40,924 alleles

Filtering AF 7e-05% ClinGen BA1/BS1 input FAF95, joint · FAF99 1.9e-05%

Overall 0.000286% 4/1,399,294 alleles · very rare

Ancestry group	Frequency	1 in
East Asiangrpmax	0.00244%	40,924
European (non-Finnish)	0.000262%	382,320

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: CAPN14
Protein: p.Val401Met
Coding: c.1201G>A
MANE Select: NM_001145122
dbSNP: rs1167740802
Type: single nucleotide variant
Location: chr2:31192012 (GRCh38)
Gene constraint: LOEUF 1.109 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 86.02
Residue 401: the 'domain iii' region

Full CAPN14 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Similar variants

CAPN14 p.Leu185= Benign ★★ same type
CAPN14 p.Ala183Thr Uncertain significance ★ ⚠ same type
CAPN14 p.Ala255Thr Uncertain significance ★ ⚠ same type
CAPN14 p.Ala35Thr Uncertain significance ★ ⚠ same type
CAPN14 p.Ala51Thr Uncertain significance ★ ⚠ same type
CAPN14 p.Ala613Val Uncertain significance ★ ⚠ same type
CAPN14 p.Arg119Gln Uncertain significance ★ ⚠ same type
CAPN14 p.Arg119Trp 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/capn14-p-val401met (accessed [today's date]).

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