Is CAPN14 p.Ala344Val (c.1031C>T) pathogenic?

CAPN14 p.Ala344Val (c.1031C>T) is classified Likely benign in CAPN14 (ClinVar, Single submitter, 1 submitter; last evaluated 2025-08-24). AlphaMissense: likely benign (0.0705); Ultra-rare (popmax 0.0137%, amr).

How common is CAPN14 p.Ala344Val (c.1031C>T) in the general population?

CAPN14 p.Ala344Val (c.1031C>T) is ultra-rare (popmax 0.0137%, amr) (gnomAD).

What do computational predictors say about CAPN14 p.Ala344Val (c.1031C>T)?

AlphaMissense predicts likely benign (score 0.0705) — an in-silico prediction, not a clinical call.

CAPN14 p.Ala344Val

c.1031C>T · VCV4218824

Likely benign Single submitter

Classification

Likely benign

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.0705 · ACMG-weighted

gnomAD v4.1

Rare

ultra-rare (popmax 0.0137%, amr)

Missense predictors

0/3 damaging

AlphaMissense, REVEL, SaProt

Computational evidence

Protein change
AlphaMissense	0.0705	likely benign
REVEL	0.089	moderately benign-leaning
SaProt	LLR -6.92	tolerated
⇒ AlphaMissense, REVEL and SaProt all call this tolerated.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP -1.2	GERP -3.8
Regional constraint	o/e 1.01	unconstrained · MANE · 31 kb · p 0.76 · regional, not allelic
Overall
CADD	0.463	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 0.0137% Admixed American · 7/50,988 alleles

Filtering AF 0.00639% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.00455%

Overall 0.00103% 16/1,551,490 alleles · ultra-rare

Ancestry group	Frequency	1 in
Admixed Americangrpmax	0.0137%	7,284
South Asian	0.00238%	42,027
Finnishnot grpmax-eligible	0.00167%	59,796
Remaining individualsnot grpmax-eligible	0.00166%	60,104
European (non-Finnish)	0.000436%	229,400

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.Ala344Val
Coding: c.1031C>T
MANE Select: NM_001145122
Type: single nucleotide variant
Location: chr2:31193214 (GRCh38)
Gene constraint: LOEUF 1.109 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 86.02
Residue 344: 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-ala344val (accessed [today's date]).

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