Is CAPN5 p.Pro61Ala (c.181C>G) pathogenic?

CAPN5 p.Pro61Ala (c.181C>G) is classified Uncertain significance in CAPN5 (ClinVar, Single submitter, 1 submitter; last evaluated 2023-02-22). AlphaMissense: ambiguous (0.4591); Absent from gnomAD v4.1; Associated with Inborn genetic diseases.

What condition is associated with CAPN5 p.Pro61Ala (c.181C>G)?

CAPN5 p.Pro61Ala (c.181C>G) is associated with Inborn genetic diseases (ClinVar).

How common is CAPN5 p.Pro61Ala (c.181C>G) in the general population?

CAPN5 p.Pro61Ala (c.181C>G) is absent from gnomAD v4.1 (gnomAD).

What do computational predictors say about CAPN5 p.Pro61Ala (c.181C>G)?

AlphaMissense predicts ambiguous (score 0.4591) — an in-silico prediction, not a clinical call.

CAPN5 p.Pro61Ala

c.181C>G · rs1555036987 · VCV2487009

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

ambiguous

0.4591 · ACMG-weighted

gnomAD v4.1

Absent

absent from gnomAD v4.1

Conditions

Inborn genetic diseases

Computational evidence

Protein change
AlphaMissense	0.4591	ambiguous
REVEL	0.553	indeterminate
SaProt	LLR -9.38	tolerated
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 7.5	GERP 1.8, phastCons 1
Regional constraint	o/e 0.89	unconstrained · MANE · 39 kb · p 0.00098 · regional, not allelic
Overall
CADD	26.6	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: CAPN5
Protein: p.Pro61Ala
Coding: c.181C>G
MANE Select: NM_004055
dbSNP: rs1555036987
Type: single nucleotide variant
Location: chr11:77093697 (GRCh38)
Gene constraint: LOEUF 0.928 · pLI <0.01 · ClinGen HI 0/3 (gnomAD)
Structure: AlphaFold pLDDT 91.71 · 1 PDB
Residue 61: the calpain catalytic domain

Full CAPN5 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

CAPN5 p.Pro61Leu Uncertain significance ★ ⚠ same residue
CAPN5 p.Pro61= Likely benign ★ same residue
CAPN5 p.Ala183Ser Uncertain significance ★★ ⚠ same condition
CAPN5 p.Ala237Val Uncertain significance ★★ ⚠ same condition
CAPN5 p.Ala253Thr Uncertain significance ★★ ⚠ same condition
CAPN5 p.Ala34Val Uncertain significance ★★ ⚠ same condition
CAPN5 p.Ala357Val Uncertain significance ★★ ⚠ same condition
CAPN5 p.Ala362Gly 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/capn5-p-pro61ala (accessed [today's date]).

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