Is CAPN10 p.Lys366Thr (c.1097A>C) pathogenic?

CAPN10 p.Lys366Thr (c.1097A>C) is classified Uncertain significance in CAPN10 (ClinVar, No assertion criteria, 1 submitter; last evaluated 2024-04-04). AlphaMissense: likely pathogenic (0.7156); Absent from gnomAD v4.1; Associated with CAPN10-related disorder.

What condition is associated with CAPN10 p.Lys366Thr (c.1097A>C)?

CAPN10 p.Lys366Thr (c.1097A>C) is associated with CAPN10-related disorder (ClinVar).

How common is CAPN10 p.Lys366Thr (c.1097A>C) in the general population?

CAPN10 p.Lys366Thr (c.1097A>C) is absent from gnomAD v4.1 (gnomAD).

What do computational predictors say about CAPN10 p.Lys366Thr (c.1097A>C)?

AlphaMissense predicts likely pathogenic (score 0.7156) — an in-silico prediction, not a clinical call.

CAPN10 p.Lys366Thr

c.1097A>C · VCV3349120

Uncertain significance No assertion criteria

Classification

Uncertain significance

ClinVar

Review

No assertion criteria ☆☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely pathogenic

0.7156 · ACMG-weighted

gnomAD v4.1

Absent

absent from gnomAD v4.1

Missense predictors

2/3 damaging

AlphaMissense, REVEL, SaProt

Conditions

CAPN10-related disorder

Computational evidence

Protein change
AlphaMissense	0.7156	likely pathogenic
REVEL	0.733	pathogenic-leaning
SaProt	LLR -9.86	tolerated
⇒ AlphaMissense and REVEL call this damaging; SaProt does not.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 11	GERP 1.1, phastCons 1
Regional constraint	o/e 0.92	unconstrained · MANE · 12 kb · p 0.013 · regional, not allelic
Overall
CADD	27.6	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

Absent from gnomAD v4.1. Not observed in any sequenced alleles — a rarity signal (ACMG PM2-supporting), not evidence of pathogenicity on its own.

Variant & gene context

Gene: CAPN10
Protein: p.Lys366Thr
Coding: c.1097A>C
MANE Select: NM_023083
Type: single nucleotide variant
Location: chr2:240595123 (GRCh38)
Gene constraint: LOEUF 1.121 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 83.91
Residue 366: the 'domain iii 1' region

Full CAPN10 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Disease context

CAPN10-related disorder

Similar variants

CAPN10 c.1989+1G>A Pathogenic ★ same condition
CAPN10 p.Ala380= Uncertain significance ★ same condition
CAPN10 p.Arg395Gln Uncertain significance ★ ⚠ same condition
CAPN10 c.1990-7T>C Benign same condition
CAPN10 p.Ala390= Likely benign same condition
CAPN10 p.Ala447= Likely benign same condition
CAPN10 p.Ala450= Likely benign same condition
CAPN10 p.Ala511= Likely benign 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-lys366thr (accessed [today's date]).

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