Is CAPN10 p.Val557Ile (c.1669G>A) pathogenic?

CAPN10 p.Val557Ile (c.1669G>A) is classified Uncertain significance in CAPN10 (ClinVar, Single submitter, 1 submitter; last evaluated 2021-04-29). AlphaMissense: likely benign (0.0786); Very rare (popmax 0.00666%, afr); Associated with Inborn genetic diseases.

What condition is associated with CAPN10 p.Val557Ile (c.1669G>A)?

CAPN10 p.Val557Ile (c.1669G>A) is associated with Inborn genetic diseases (ClinVar).

How common is CAPN10 p.Val557Ile (c.1669G>A) in the general population?

CAPN10 p.Val557Ile (c.1669G>A) is very rare (popmax 0.00666%, afr) (gnomAD).

What do computational predictors say about CAPN10 p.Val557Ile (c.1669G>A)?

AlphaMissense predicts likely benign (score 0.0786) — an in-silico prediction, not a clinical call.

CAPN10 p.Val557Ile

c.1669G>A · rs747049929 · VCV2340975

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.0786 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 0.00666%, afr)

Missense predictors

0/3 damaging

AlphaMissense, REVEL, SaProt

Conditions

Inborn genetic diseases

Computational evidence

Protein change
AlphaMissense	0.0786	likely benign
REVEL	0.146	moderately benign-leaning
SaProt	LLR -9.01	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 -0.079	GERP -2.9
Regional constraint	o/e 0.92	unconstrained · MANE · 12 kb · p 0.013 · regional, not allelic
Overall
CADD	9.604	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 0.00666% African / African-American · 5/75,056 alleles

Filtering AF 0.00435% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.00396%

Overall 0.00483% 78/1,613,578 alleles · very rare

Ancestry group	Frequency	1 in
African / African-Americangrpmax	0.00666%	15,011
European (non-Finnish)	0.00542%	18,438
Remaining individualsnot grpmax-eligible	0.0048%	20,835
South Asian	0.00329%	30,361
Finnishnot grpmax-eligible	0.00315%	31,714
Admixed American	0.00167%	60,022

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: CAPN10
Protein: p.Val557Ile
Coding: c.1669G>A
MANE Select: NM_023083
dbSNP: rs747049929
Type: single nucleotide variant
Location: chr2:240596868 (GRCh38)
Gene constraint: LOEUF 1.121 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 83.91
Residue 557: the 'domain iii 2' region

Full CAPN10 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

Similar variants

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CAPN10 p.Gly526Ser Uncertain significance ★★ ⚠ same condition
CAPN10 p.Pro46Ser Uncertain significance ★★ ⚠ same condition
CAPN10 p.Thr339Met Uncertain significance ★★ ⚠ same condition
CAPN10 p.Ala156Thr Uncertain significance ★ ⚠ same condition
CAPN10 p.Ala252Val Uncertain significance ★ ⚠ same condition
CAPN10 p.Ala341Thr Uncertain significance ★ ⚠ same condition
CAPN10 p.Ala389Val 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/capn10-p-val557ile (accessed [today's date]).

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