Is CAPN3 p.Val811Ile (c.2431G>A) pathogenic?

CAPN3 p.Val811Ile (c.2431G>A) is classified Uncertain significance in CAPN3 (ClinVar, Multiple submitters, 3 submitters; last evaluated 2025-05-11). AlphaMissense: likely benign (0.1452); Very rare (popmax 0.00446%, eas); Associated with Inborn genetic diseases.

What condition is associated with CAPN3 p.Val811Ile (c.2431G>A)?

CAPN3 p.Val811Ile (c.2431G>A) is associated with Inborn genetic diseases, autosomal recessive limb-girdle muscular dystrophy type 2A (ClinVar).

How common is CAPN3 p.Val811Ile (c.2431G>A) in the general population?

CAPN3 p.Val811Ile (c.2431G>A) is very rare (popmax 0.00446%, eas) (gnomAD).

What do computational predictors say about CAPN3 p.Val811Ile (c.2431G>A)?

AlphaMissense predicts likely benign (score 0.1452) — an in-silico prediction, not a clinical call.

CAPN3 p.Val811Ile

c.2431G>A · rs200516941 · VCV290293

Uncertain significance Multiple submitters

Classification

Uncertain significance

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 3 submitters

AlphaMissense

likely benign

0.1452 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 0.00446%, eas)

Missense predictors

0/2 damaging

AlphaMissense, SaProt · REVEL no call

Conditions

Inborn genetic diseases

Computational evidence

Protein change
AlphaMissense	0.1452	likely benign
REVEL	0.485	indeterminate
SaProt	LLR -7.44	tolerated
⇒ AlphaMissense and SaProt both call this tolerated; REVEL makes no call.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 12	GERP 2.9, phastCons 1
Regional constraint	o/e 0.96	unconstrained · MANE · 52 kb · p 0.21 · regional, not allelic
Overall
CADD	28.1	PHRED · no single calibrated threshold — expert panels disagree

ClinVar classifies this uncertain; the computational predictors unanimously lean tolerated — a triage signal, not a reclassification

AlphaMissense carries the ACMG weight for missense; REVEL and SaProt are independent agreement signals.

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.00446% East Asian · 2/44,866 alleles

Filtering AF 0.000739% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.000366%

Overall 0.00109% 16/1,461,758 alleles · very rare

Ancestry group	Frequency	1 in
East Asiangrpmax	0.00446%	22,433
Remaining individualsnot grpmax-eligible	0.0032%	31,252
Admixed American	0.00167%	60,020
European (non-Finnish)	0.000932%	107,264

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: CAPN3
Protein: p.Val811Ile
Coding: c.2431G>A
MANE Select: NM_000070
dbSNP: rs200516941
Type: single nucleotide variant
Location: chr15:42411337 (GRCh38)
Gene constraint: LOEUF 0.896 · pLI <0.01 · ClinGen HI gene assoc. with recessive phenotype (gnomAD)
Structure: AlphaFold pLDDT 79.18 · 5 PDB
Residue 811: the 'domain iv' region; an α-helix; the ef-hand 4 domain

Full CAPN3 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: autosomal recessive limb-girdle muscular dystrophy type 2A

Similar variants

CAPN3 p.Val811= Benign/Likely benign ★★ same residue
CAPN3 p.Val811Leu Uncertain significance ★ ⚠ same residue
CAPN3 c.1115+5G>C Pathogenic ★★★ same condition
CAPN3 c.1194-2A>G Pathogenic ★★★ same condition
CAPN3 c.1194-9A>G Pathogenic ★★★ same condition
CAPN3 c.1746-20C>G Pathogenic ★★★ same condition
CAPN3 c.1993-1G>A Pathogenic ★★★ same condition
CAPN3 c.499-1G>A Pathogenic ★★★ 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/capn3-p-val811ile (accessed [today's date]).

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