Is CAPN13 p.Asp44His (c.130G>C) pathogenic?

CAPN13 p.Asp44His (c.130G>C) is classified Uncertain significance in CAPN13 (ClinVar, Single submitter, 1 submitter; last evaluated 2025-08-03). AlphaMissense: likely benign (0.1291); Very rare (popmax 0.00134%, afr).

How common is CAPN13 p.Asp44His (c.130G>C) in the general population?

CAPN13 p.Asp44His (c.130G>C) is very rare (popmax 0.00134%, afr) (gnomAD).

What do computational predictors say about CAPN13 p.Asp44His (c.130G>C)?

AlphaMissense predicts likely benign (score 0.1291) — an in-silico prediction, not a clinical call.

CAPN13 p.Asp44His

c.130G>C · VCV4218811

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.1291 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 0.00134%, afr)

Missense predictors

0/2 damaging

AlphaMissense, SaProt · REVEL no call

Computational evidence

Protein change
AlphaMissense	0.1291	likely benign
REVEL	0.418	indeterminate
SaProt	LLR -7.75	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 -0.93	GERP -4.6
Regional constraint	o/e 1.05	unconstrained · MANE · 57 kb · p 0.12 · regional, not allelic
Overall
CADD	9.996	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 0.00134% African / African-American · 1/74,740 alleles

Overall 0.000125% 2/1,602,052 alleles · very rare

Ancestry group	Frequency	1 in
African / African-Americangrpmax	0.00134%	74,740
European (non-Finnish)	8.51e-05%	1,174,406

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: CAPN13
Protein: p.Asp44His
Coding: c.130G>C
MANE Select: NM_144575
Type: single nucleotide variant
Location: chr2:30787196 (GRCh38)
Gene constraint: LOEUF 1.121 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 83.25 · 1 PDB
Residue 44: the calpain catalytic domain

Full CAPN13 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Similar variants

CAPN13 p.Ala172Ser Uncertain significance ★ ⚠ same type
CAPN13 p.Ala215Ser Uncertain significance ★ ⚠ same type
CAPN13 p.Ala2Val Uncertain significance ★ ⚠ same type
CAPN13 p.Ala326Val Uncertain significance ★ ⚠ same type
CAPN13 p.Ala460Gly Uncertain significance ★ ⚠ same type
CAPN13 p.Ala510Pro Uncertain significance ★ ⚠ same type
CAPN13 p.Ala564Val Uncertain significance ★ ⚠ same type
CAPN13 p.Ala90Ser 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/capn13-p-asp44his (accessed [today's date]).

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