Is CAPN10 p.Trp302Ter (c.905G>A) pathogenic?

CAPN10 p.Trp302Ter (c.905G>A) is classified Likely pathogenic in CAPN10 (ClinVar, Single submitter, 1 submitter; last evaluated 2025-11-19). Very rare (popmax 8.47e-05%, nfe); Associated with diabetes mellitus, noninsulin-dependent, 1.

What condition is associated with CAPN10 p.Trp302Ter (c.905G>A)?

CAPN10 p.Trp302Ter (c.905G>A) is associated with diabetes mellitus, noninsulin-dependent, 1 (ClinVar).

How common is CAPN10 p.Trp302Ter (c.905G>A) in the general population?

CAPN10 p.Trp302Ter (c.905G>A) is very rare (popmax 8.47e-05%, nfe) (gnomAD).

CAPN10 p.Trp302Ter

c.905G>A · VCV4533287

Likely pathogenic Single submitter

Classification

Likely pathogenic

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

Consequence

nonsense (stop-gain)

predicted LoF

gnomAD v4.1

Rare

very rare (popmax 8.47e-05%, nfe)

Conditions

diabetes mellitus, noninsulin-dependent, 1

Computational evidence

Protein change
Missense predictors do not apply to this variant type; conservation carries the signal.
Consequence	nonsense (stop-gain)	predicted loss-of-function
NMD	predicted	premature termination codon in exon 6 of 12
Splicing
SpliceAI	<0.2	all four deltas below 0.2 · G>C here scores Δ0.23 · evaluated, not missing
Constraint at this position
Conservation	phyloP 12	GERP 1.3, phastCons 1
Overall
CADD	47.0	PHRED · no single calibrated threshold — expert panels disagree

Predicted loss-of-function is descriptive, not an applied PVS1 code.

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 8.47e-05% European (non-Finnish) · 1/1,180,000 alleles

Overall 6.84e-05% 1/1,461,702 alleles · very rare

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.Trp302Ter
Coding: c.905G>A
MANE Select: NM_023083
Type: single nucleotide variant
Location: chr2:240594617 (GRCh38)
Gene constraint: LOEUF 1.121 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 83.91
Residue 302: the calpain catalytic domain

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

Disease context

diabetes mellitus, noninsulin-dependent, 1 — disease report on Sugi Atlas → Associated genes, phenotypes, clinical trials & treatments

Similar variants

CAPN10 p.Pro574Ala Uncertain significance ★ ⚠ same condition
CAPN10 p.Arg127Cys Uncertain significance ★★ ⚠ same type
CAPN10 p.Gly526Ser Uncertain significance ★★ ⚠ same type
CAPN10 p.Pro46Ser Uncertain significance ★★ ⚠ same type
CAPN10 p.Thr339Met Uncertain significance ★★ ⚠ same type
CAPN10 p.Ala477= Benign ★★ same type
CAPN10 p.Ala477Thr Benign ★★ same type
CAPN10 p.Arg555Cys Likely benign ★★ 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/capn10-p-trp302ter (accessed [today's date]).

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