Is CAPN5 p.Asp203Val (c.608A>T) pathogenic?

CAPN5 p.Asp203Val (c.608A>T) is classified Uncertain significance in CAPN5 (ClinVar, Single submitter, 1 submitter; last evaluated 2024-05-02). AlphaMissense: likely benign (0.15); Absent from gnomAD v4.1.

How common is CAPN5 p.Asp203Val (c.608A>T) in the general population?

CAPN5 p.Asp203Val (c.608A>T) is absent from gnomAD v4.1 (gnomAD).

What do computational predictors say about CAPN5 p.Asp203Val (c.608A>T)?

AlphaMissense predicts likely benign (score 0.15) — an in-silico prediction, not a clinical call.

CAPN5 p.Asp203Val

c.608A>T · VCV3651899

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.15 · ACMG-weighted

gnomAD v4.1

Absent

absent from gnomAD v4.1

Missense predictors

1/2 damaging

AlphaMissense, SaProt · REVEL no call

Computational evidence

Protein change
AlphaMissense	0.15	likely benign
REVEL	0.368	indeterminate
SaProt	LLR -11.58	damaging
⇒ SaProt calls this damaging; AlphaMissense does not; REVEL makes no call.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 8	GERP 0.95, phastCons 1
Regional constraint	o/e 0.89	unconstrained · MANE · 39 kb · p 0.00098 · regional, not allelic
Overall
CADD	19.4	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.Asp203Val
Coding: c.608A>T
MANE Select: NM_004055
Type: single nucleotide variant
Location: chr11:77114343 (GRCh38)
Gene constraint: LOEUF 0.928 · pLI <0.01 · ClinGen HI 0/3 (gnomAD)
Structure: AlphaFold pLDDT 91.71 · 1 PDB
Residue 203: the calpain catalytic domain

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

Similar variants

CAPN5 p.Asp203Ala 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-asp203val (accessed [today's date]).

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