Is CAPN3 p.Ser202Ile (c.605G>T) pathogenic?

CAPN3 p.Ser202Ile (c.605G>T) is classified Uncertain significance in CAPN3 (ClinVar, Single submitter, 1 submitter; last evaluated 2022-04-22). AlphaMissense: likely pathogenic (0.9518); Absent from gnomAD v4.1; Associated with Inborn genetic diseases.

What condition is associated with CAPN3 p.Ser202Ile (c.605G>T)?

CAPN3 p.Ser202Ile (c.605G>T) is associated with Inborn genetic diseases (ClinVar).

How common is CAPN3 p.Ser202Ile (c.605G>T) in the general population?

CAPN3 p.Ser202Ile (c.605G>T) is absent from gnomAD v4.1 (gnomAD).

What do computational predictors say about CAPN3 p.Ser202Ile (c.605G>T)?

AlphaMissense predicts likely pathogenic (score 0.9518) — an in-silico prediction, not a clinical call.

CAPN3 p.Ser202Ile

c.605G>T · rs2548258110 · VCV2285091

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely pathogenic

0.9518 · ACMG-weighted

gnomAD v4.1

Absent

absent from gnomAD v4.1

Missense predictors

3/3 damaging

AlphaMissense, REVEL, SaProt

Conditions

Inborn genetic diseases

Computational evidence

Protein change
AlphaMissense	0.9518	likely pathogenic
REVEL	0.912	moderately pathogenic-leaning
SaProt	LLR -10.79	damaging
⇒ AlphaMissense, REVEL and SaProt all call this damaging.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 12	GERP 2.8, phastCons 1
Regional constraint	o/e 0.96	unconstrained · MANE · 52 kb · p 0.21 · regional, not allelic
Overall
CADD	29.8	PHRED · no single calibrated threshold — expert panels disagree

ClinVar classifies this uncertain; the computational predictors unanimously lean damaging — 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

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: CAPN3
Protein: p.Ser202Ile
Coding: c.605G>T
MANE Select: NM_000070
dbSNP: rs2548258110
Type: single nucleotide variant
Location: chr15:42387859 (GRCh38)
Gene constraint: LOEUF 0.896 · pLI <0.01 · ClinGen HI gene assoc. with recessive phenotype (gnomAD)
Structure: AlphaFold pLDDT 79.18 · 5 PDB
Residue 202: the calpain catalytic domain; an α-helix; a UniProt-annotated variant site (in lgmdr1)

Full CAPN3 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

CAPN3 p.Ser202= Benign/Likely benign ★★ same residue
CAPN3 p.Ala14Val Uncertain significance ★★ ⚠ same condition
CAPN3 p.Ala335Thr Uncertain significance ★★ ⚠ same condition
CAPN3 p.Ala34Pro Uncertain significance ★★ ⚠ same condition
CAPN3 p.Ala385Val Uncertain significance ★★ ⚠ same condition
CAPN3 p.Ala750Val Uncertain significance ★★ ⚠ same condition
CAPN3 p.Arg386His Uncertain significance ★★ ⚠ same condition
CAPN3 p.Asn195Ser 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/capn3-p-ser202ile (accessed [today's date]).

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