Is CAPN7 p.Ile286Val (c.856A>G) pathogenic?

CAPN7 p.Ile286Val (c.856A>G) is classified Uncertain significance in CAPN7 (ClinVar, Single submitter, 1 submitter; last evaluated 2025-12-11). AlphaMissense: likely benign (0.0566); Ultra-rare (popmax 0.0165%, mid).

How common is CAPN7 p.Ile286Val (c.856A>G) in the general population?

CAPN7 p.Ile286Val (c.856A>G) is ultra-rare (popmax 0.0165%, mid) (gnomAD).

What do computational predictors say about CAPN7 p.Ile286Val (c.856A>G)?

AlphaMissense predicts likely benign (score 0.0566) — an in-silico prediction, not a clinical call.

CAPN7 p.Ile286Val

c.856A>G · VCV4648149

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.0566 · ACMG-weighted

gnomAD v4.1

Rare

ultra-rare (popmax 0.0165%, mid)

Missense predictors

0/2 damaging

AlphaMissense, SaProt · REVEL no call

Computational evidence

Protein change
AlphaMissense	0.0566	likely benign
REVEL	0.342	indeterminate
SaProt	LLR -1.56	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 11	GERP 1.8, phastCons 1
Regional constraint	o/e 0.88	unconstrained · MANE · 28 kb · p 0.0017 · regional, not allelic
Overall
CADD	20.5	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 0.0165% Middle Eastern · 1/6,048 alleles

Filtering AF 0.00665% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.00485%

Overall 0.00461% 74/1,606,272 alleles · ultra-rare

Ancestry group	Frequency	1 in
Middle Easterngrpmax	0.0165%	6,048
Admixed American	0.0134%	7,452
African / African-American	0.0107%	9,361
South Asian	0.00554%	18,050
East Asian	0.00447%	22,351
European (non-Finnish)	0.00409%	24,461
Remaining individualsnot grpmax-eligible	0.00322%	31,099

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: CAPN7
Protein: p.Ile286Val
Coding: c.856A>G
MANE Select: NM_014296
Type: single nucleotide variant
Location: chr3:15228977 (GRCh38)
Gene constraint: LOEUF 0.882 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 88.88 · 2 PDB
Residue 286: the calpain catalytic domain

Full CAPN7 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Similar variants

CAPN7 c.2073+1G>T Uncertain significance ★ same type
CAPN7 p.Ala10Asp Uncertain significance ★ ⚠ same type
CAPN7 p.Ala10Ser Uncertain significance ★ ⚠ same type
CAPN7 p.Ala149Val Uncertain significance ★ ⚠ same type
CAPN7 p.Ala29Val Uncertain significance ★ ⚠ same type
CAPN7 p.Ala37Thr Uncertain significance ★ ⚠ same type
CAPN7 p.Ala39Asp Uncertain significance ★ ⚠ same type
CAPN7 p.Ala459Ser 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/capn7-p-ile286val (accessed [today's date]).

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