Is CAPN5 p.Phe272Val (c.814T>G) pathogenic?

CAPN5 p.Phe272Val (c.814T>G) is classified Uncertain significance in CAPN5 (ClinVar, Multiple submitters, 2 submitters; last evaluated 2025-09-12). AlphaMissense: likely pathogenic (0.6357); Very rare (popmax 0.00333%, amr).

How common is CAPN5 p.Phe272Val (c.814T>G) in the general population?

CAPN5 p.Phe272Val (c.814T>G) is very rare (popmax 0.00333%, amr) (gnomAD).

What do computational predictors say about CAPN5 p.Phe272Val (c.814T>G)?

AlphaMissense predicts likely pathogenic (score 0.6357) — an in-silico prediction, not a clinical call.

CAPN5 p.Phe272Val

c.814T>G · rs1003325364 · VCV2161357

Uncertain significance Multiple submitters

Classification

Uncertain significance

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 2 submitters

AlphaMissense

likely pathogenic

0.6357 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 0.00333%, amr)

Missense predictors

1/2 damaging

AlphaMissense, SaProt · REVEL no call

Computational evidence

Protein change
AlphaMissense	0.6357	likely pathogenic
REVEL	0.419	indeterminate
SaProt	LLR -8.41	tolerated
⇒ AlphaMissense calls this damaging; SaProt does not; REVEL makes no call.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 7.8	GERP 1.9, phastCons 1
Regional constraint	o/e 0.89	unconstrained · MANE · 39 kb · p 0.00098 · regional, not allelic
Overall
CADD	28.3	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 0.00333% Admixed American · 2/60,032 alleles

Filtering AF 0.000553% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.000207%

Overall 0.000274% 4/1,461,008 alleles · very rare

Ancestry group	Frequency	1 in
Admixed Americangrpmax	0.00333%	30,016
European (non-Finnish)	0.000169%	590,002

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: CAPN5
Protein: p.Phe272Val
Coding: c.814T>G
MANE Select: NM_004055
dbSNP: rs1003325364
Type: single nucleotide variant
Location: chr11:77115509 (GRCh38)
Gene constraint: LOEUF 0.928 · pLI <0.01 · ClinGen HI 0/3 (gnomAD)
Structure: AlphaFold pLDDT 91.71 · 1 PDB
Residue 272: the calpain catalytic domain; an α-helix

Full CAPN5 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Similar variants

CAPN5 p.Phe272Leu Uncertain significance ★★ ⚠ same residue
CAPN5 p.Phe272del Uncertain significance ★ same residue
CAPN5 p.Arg243Leu Pathogenic ★★ ⚠ same type
CAPN5 p.Arg289Trp Pathogenic ★★ ⚠ same type
CAPN5 p.Ala118Val Uncertain significance ★★ ⚠ same type
CAPN5 p.Ala183Ser Uncertain significance ★★ ⚠ same type
CAPN5 p.Ala185Val Uncertain significance ★★ ⚠ same type
CAPN5 p.Ala237Val 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/capn5-p-phe272val (accessed [today's date]).

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