Is CAPN5 p.Asp110Glu (c.330C>A) pathogenic?

CAPN5 p.Asp110Glu (c.330C>A) is classified Uncertain significance in CAPN5 (ClinVar, Single submitter, 1 submitter; last evaluated 2022-03-09). AlphaMissense: likely benign (0.1599); Very rare (popmax 0.00133%, afr).

How common is CAPN5 p.Asp110Glu (c.330C>A) in the general population?

CAPN5 p.Asp110Glu (c.330C>A) is very rare (popmax 0.00133%, afr) (gnomAD).

What do computational predictors say about CAPN5 p.Asp110Glu (c.330C>A)?

AlphaMissense predicts likely benign (score 0.1599) — an in-silico prediction, not a clinical call.

CAPN5 p.Asp110Glu

c.330C>A · rs1950422986 · VCV1499864

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.1599 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 0.00133%, afr)

Missense predictors

1/3 damaging

AlphaMissense, REVEL, SaProt

Computational evidence

Protein change
AlphaMissense	0.1599	likely benign
REVEL	0.05	moderately benign-leaning
SaProt	LLR -10.58	damaging
⇒ SaProt calls this damaging; AlphaMissense and REVEL do not.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 1.4	GERP -0.63, phastCons 1
Regional constraint	o/e 0.89	unconstrained · MANE · 39 kb · p 0.00098 · regional, not allelic
Overall
CADD	18.39	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

Grpmax group 0.00133% African / African-American · 1/74,924 alleles

Overall 0.000657% 1/152,166 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: CAPN5
Protein: p.Asp110Glu
Coding: c.330C>A
MANE Select: NM_004055
dbSNP: rs1950422986
Type: single nucleotide variant
Location: chr11:77112621 (GRCh38)
Gene constraint: LOEUF 0.928 · pLI <0.01 · ClinGen HI 0/3 (gnomAD)
Structure: AlphaFold pLDDT 91.71 · 1 PDB
Residue 110: the calpain catalytic domain

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

Similar variants

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
CAPN5 p.Ala253Thr 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-asp110glu (accessed [today's date]).

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