Is CAPN5 p.Asp60Glu (c.180C>A) pathogenic?

CAPN5 p.Asp60Glu (c.180C>A) is classified Uncertain significance in CAPN5 (ClinVar, Multiple submitters, 2 submitters; last evaluated 2025-12-25). AlphaMissense: likely benign (0.1473); Very rare (popmax 0.00187%, nfe).

How common is CAPN5 p.Asp60Glu (c.180C>A) in the general population?

CAPN5 p.Asp60Glu (c.180C>A) is very rare (popmax 0.00187%, nfe) (gnomAD).

What do computational predictors say about CAPN5 p.Asp60Glu (c.180C>A)?

AlphaMissense predicts likely benign (score 0.1473) — an in-silico prediction, not a clinical call.

CAPN5 p.Asp60Glu

c.180C>A · rs782370432 · VCV838836

Uncertain significance Multiple submitters

Classification

Uncertain significance

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 2 submitters

AlphaMissense

likely benign

0.1473 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 0.00187%, nfe)

Missense predictors

0/2 damaging

AlphaMissense, SaProt · REVEL no call

Computational evidence

Protein change
AlphaMissense	0.1473	likely benign
REVEL	0.362	indeterminate
SaProt	LLR -6.62	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 0.54	GERP 0.68, phastCons 1
Regional constraint	o/e 0.89	unconstrained · MANE · 39 kb · p 0.00098 · regional, not allelic
Overall
CADD	17.37	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 0.00187% European (non-Finnish) · 22/1,175,958 alleles

Filtering AF 0.00122% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.00105%

Overall 0.00144% 23/1,600,676 alleles · very rare

Ancestry group	Frequency	1 in
European (non-Finnish)grpmax	0.00187%	53,452
Remaining individualsnot grpmax-eligible	0.00161%	62,090

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: CAPN5
Protein: p.Asp60Glu
Coding: c.180C>A
MANE Select: NM_004055
dbSNP: rs782370432
Type: single nucleotide variant
Location: chr11:77093696 (GRCh38)
Gene constraint: LOEUF 0.928 · pLI <0.01 · ClinGen HI 0/3 (gnomAD)
Structure: AlphaFold pLDDT 91.71 · 1 PDB
Residue 60: the calpain catalytic domain; a β-strand

Full CAPN5 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Similar variants

CAPN5 p.Asp60Gly Uncertain significance ★★ ⚠ same residue
CAPN5 p.Arg243Leu Pathogenic ★★ ⚠ same type
CAPN5 p.Arg289Trp Pathogenic ★★ ⚠ same type
CAPN5 p.Ala118Val Uncertain significance ★★ ⚠ same type
CAPN5 p.Ala183Ser Uncertain significance ★★ ⚠ same type
CAPN5 p.Ala185Val Uncertain significance ★★ ⚠ same type
CAPN5 p.Ala237Val Uncertain significance ★★ ⚠ same type
CAPN5 p.Ala245Val 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/capn5-p-asp60glu (accessed [today's date]).

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