Is CAPN14 p.Val163Phe (c.487G>T) pathogenic?

CAPN14 p.Val163Phe (c.487G>T) is classified Uncertain significance in CAPN14 (ClinVar, Single submitter, 1 submitter; last evaluated 2025-04-06). AlphaMissense: likely benign (0.3337); Ultra-rare (popmax 0.0122%, eas).

How common is CAPN14 p.Val163Phe (c.487G>T) in the general population?

CAPN14 p.Val163Phe (c.487G>T) is ultra-rare (popmax 0.0122%, eas) (gnomAD).

What do computational predictors say about CAPN14 p.Val163Phe (c.487G>T)?

AlphaMissense predicts likely benign (score 0.3337) — an in-silico prediction, not a clinical call.

CAPN14 p.Val163Phe

c.487G>T · VCV3995193

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.3337 · ACMG-weighted

gnomAD v4.1

Rare

ultra-rare (popmax 0.0122%, eas)

Missense predictors

1/3 damaging

AlphaMissense, REVEL, SaProt

Computational evidence

Protein change
AlphaMissense	0.3337	likely benign
REVEL	0.278	benign-leaning
SaProt	LLR -10.76	damaging
⇒ SaProt calls this damaging; AlphaMissense and REVEL do not.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP -1.1	GERP -4.1
Regional constraint	o/e 1.01	unconstrained · MANE · 31 kb · p 0.76 · regional, not allelic
Overall
CADD	16.72	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 0.0122% East Asian · 5/40,908 alleles

Filtering AF 0.00479% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.00309%

Overall 0.000387% 6/1,551,714 alleles · ultra-rare

Ancestry group	Frequency	1 in
East Asiangrpmax	0.0122%	8,182
Remaining individualsnot grpmax-eligible	0.00166%	60,120

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.Val163Phe
Coding: c.487G>T
MANE Select: NM_001145122
Type: single nucleotide variant
Location: chr2:31201926 (GRCh38)
Gene constraint: LOEUF 1.109 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 86.02
Residue 163: the calpain catalytic domain

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-val163phe (accessed [today's date]).

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