Is CAPN5 p.Val317Met (c.949G>A) pathogenic?

CAPN5 p.Val317Met (c.949G>A) is classified Conflicting classifications of pathogenicity in CAPN5 (ClinVar, Conflicting submitters, 5 submitters; last evaluated 2025-05-11). AlphaMissense: ambiguous (0.3793); Very rare (popmax 0.00949%, nfe); Associated with Inborn genetic diseases.

What condition is associated with CAPN5 p.Val317Met (c.949G>A)?

CAPN5 p.Val317Met (c.949G>A) is associated with Inborn genetic diseases, inherited retinal dystrophy (ClinVar).

How common is CAPN5 p.Val317Met (c.949G>A) in the general population?

CAPN5 p.Val317Met (c.949G>A) is very rare (popmax 0.00949%, nfe) (gnomAD).

What do computational predictors say about CAPN5 p.Val317Met (c.949G>A)?

AlphaMissense predicts ambiguous (score 0.3793) — an in-silico prediction, not a clinical call.

CAPN5 p.Val317Met

c.949G>A · rs782495056 · VCV546683

Conflicting classifications of pathogenicity Conflicting submitters

Classification

Conflicting classifications of pathogenicity

ClinVar

Review

Conflicting submitters ★☆☆☆

ClinVar · 5 submitters

AlphaMissense

ambiguous

0.3793 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 0.00949%, nfe)

Missense predictors

0/2 damaging

REVEL, SaProt · AlphaMissense no call

Conditions

Inborn genetic diseases

Computational evidence

Protein change
AlphaMissense	0.3793	ambiguous
REVEL	0.133	moderately benign-leaning
SaProt	LLR -7.66	tolerated
⇒ REVEL and SaProt both call this tolerated; AlphaMissense makes no call.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 9.9	GERP -0.71, phastCons 1
Regional constraint	o/e 0.89	unconstrained · MANE · 39 kb · p 0.00098 · regional, not allelic
Overall
CADD	32.0	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 0.00949% European (non-Finnish) · 112/1,179,736 alleles

Filtering AF 0.00804% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.00752%

Overall 0.00756% 122/1,613,350 alleles · very rare

Ancestry group	Frequency	1 in
European (non-Finnish)grpmax	0.00949%	10,533
Remaining individualsnot grpmax-eligible	0.00801%	12,491
Admixed American	0.00667%	14,985
African / African-American	0.00133%	74,918

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.Val317Met
Coding: c.949G>A
MANE Select: NM_004055
dbSNP: rs782495056
Type: single nucleotide variant
Location: chr11:77116281 (GRCh38)
Gene constraint: LOEUF 0.928 · pLI <0.01 · ClinGen HI 0/3 (gnomAD)
Structure: AlphaFold pLDDT 91.71 · 1 PDB
Residue 317: the calpain catalytic domain

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

Disease context

Inborn genetic diseases — disease report on Sugi Atlas → Associated genes, phenotypes, clinical trials & treatments

Also linked: inherited retinal dystrophy

Similar variants

CAPN5 p.Ala183Ser Uncertain significance ★★ ⚠ same condition
CAPN5 p.Ala237Val Uncertain significance ★★ ⚠ same condition
CAPN5 p.Ala253Thr Uncertain significance ★★ ⚠ same condition
CAPN5 p.Ala34Val Uncertain significance ★★ ⚠ same condition
CAPN5 p.Ala357Val Uncertain significance ★★ ⚠ same condition
CAPN5 p.Ala362Gly Uncertain significance ★★ ⚠ same condition
CAPN5 p.Ala447Thr Uncertain significance ★★ ⚠ same condition
CAPN5 p.Ala552Ser Uncertain significance ★★ ⚠ same condition

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-val317met (accessed [today's date]).

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