Is CAPN13 p.Ser247Arg (c.741T>A) pathogenic?

CAPN13 p.Ser247Arg (c.741T>A) is classified Uncertain significance in CAPN13 (ClinVar, Single submitter, 1 submitter; last evaluated 2023-01-23). AlphaMissense: ambiguous (0.503); Absent from gnomAD v4.1.

How common is CAPN13 p.Ser247Arg (c.741T>A) in the general population?

CAPN13 p.Ser247Arg (c.741T>A) is absent from gnomAD v4.1 (gnomAD).

What do computational predictors say about CAPN13 p.Ser247Arg (c.741T>A)?

AlphaMissense predicts ambiguous (score 0.503) — an in-silico prediction, not a clinical call.

CAPN13 p.Ser247Arg

c.741T>A · rs2465773615 · VCV2477747

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

ambiguous

0.503 · ACMG-weighted

gnomAD v4.1

Absent

absent from gnomAD v4.1

Computational evidence

Protein change
AlphaMissense	0.503	ambiguous
REVEL	0.354	indeterminate
SaProt	LLR -9.68	tolerated
Splicing
SpliceAI	Δ0.68	donor loss, 6 bp away · masked 0 · deltas
Constraint at this position
Conservation	phyloP 0.081	GERP -4.2
Regional constraint	o/e 1.05	unconstrained · MANE · 57 kb · p 0.12 · regional, not allelic
Overall
CADD	15.93	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: CAPN13
Protein: p.Ser247Arg
Coding: c.741T>A
MANE Select: NM_144575
dbSNP: rs2465773615
Type: single nucleotide variant
Location: chr2:30763115 (GRCh38)
Gene constraint: LOEUF 1.121 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 83.25 · 1 PDB
Residue 247: 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-ser247arg (accessed [today's date]).

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