Is CAPN1 p.Arg343Pro (c.1028G>C) pathogenic?

CAPN1 p.Arg343Pro (c.1028G>C) is classified Uncertain significance in CAPN1 (ClinVar, Single submitter, 1 submitter; last evaluated 2025-04-25). AlphaMissense: likely pathogenic (0.9663); Absent from gnomAD v4.1; Associated with Inborn genetic diseases.

What condition is associated with CAPN1 p.Arg343Pro (c.1028G>C)?

CAPN1 p.Arg343Pro (c.1028G>C) is associated with Inborn genetic diseases (ClinVar).

How common is CAPN1 p.Arg343Pro (c.1028G>C) in the general population?

CAPN1 p.Arg343Pro (c.1028G>C) is absent from gnomAD v4.1 (gnomAD).

What do computational predictors say about CAPN1 p.Arg343Pro (c.1028G>C)?

AlphaMissense predicts likely pathogenic (score 0.9663) — an in-silico prediction, not a clinical call.

CAPN1 p.Arg343Pro

c.1028G>C · VCV3995116

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely pathogenic

0.9663 · ACMG-weighted

gnomAD v4.1

Absent

absent from gnomAD v4.1

Missense predictors

2/2 damaging

AlphaMissense, SaProt · REVEL no call

Conditions

Inborn genetic diseases

Computational evidence

Protein change
AlphaMissense	0.9663	likely pathogenic
REVEL	0.452	indeterminate
SaProt	LLR -12.18	damaging
⇒ AlphaMissense and SaProt both call this damaging; REVEL makes no call.
Splicing
SpliceAI	<0.2	all four deltas below 0.2 · G>A here scores Δ0.25 · evaluated, not missing
Constraint at this position
Conservation	phyloP 3.4	GERP -0.68, phastCons 1
Regional constraint	o/e 0.85	unconstrained · MANE · 29 kb · p 4.3e-06 · regional, not allelic
Overall
CADD	27.7	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: CAPN1
Protein: p.Arg343Pro
Coding: c.1028G>C
MANE Select: NM_005186
Type: single nucleotide variant
Location: chr11:65188609 (GRCh38)
Gene constraint: LOEUF 0.977 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 90.03 · 5 PDB
Residue 343: the calpain catalytic domain; an α-helix

Full CAPN1 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

CAPN1 p.Arg343Gln Uncertain significance ★ ⚠ same residue
CAPN1 p.Arg104His Uncertain significance ★★ ⚠ same condition
CAPN1 p.Arg293Gln Uncertain significance ★★ ⚠ same condition
CAPN1 p.Arg293Trp Uncertain significance ★★ ⚠ same condition
CAPN1 p.Arg347Cys Uncertain significance ★★ ⚠ same condition
CAPN1 p.Arg347His Uncertain significance ★★ ⚠ same condition
CAPN1 p.Arg48Gln Uncertain significance ★★ ⚠ same condition
CAPN1 p.Arg581Gln 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/capn1-p-arg343pro (accessed [today's date]).

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