Is CAPN1 p.Ala23Val (c.68C>T) pathogenic?

CAPN1 p.Ala23Val (c.68C>T) is classified Uncertain significance in CAPN1 (ClinVar, Single submitter, 1 submitter; last evaluated 2024-11-04). AlphaMissense: likely benign (0.2359); Absent from gnomAD v4.1.

How common is CAPN1 p.Ala23Val (c.68C>T) in the general population?

CAPN1 p.Ala23Val (c.68C>T) is absent from gnomAD v4.1 (gnomAD).

What do computational predictors say about CAPN1 p.Ala23Val (c.68C>T)?

AlphaMissense predicts likely benign (score 0.2359) — an in-silico prediction, not a clinical call.

CAPN1 p.Ala23Val

c.68C>T · rs2137305477 · VCV2083694

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.2359 · ACMG-weighted

gnomAD v4.1

Not reported

no allele count reported in gnomAD v4.1 (AN 1,581,336)

Missense predictors

0/3 damaging

AlphaMissense, REVEL, SaProt

Computational evidence

Protein change
AlphaMissense	0.2359	likely benign
REVEL	0.043	moderately benign-leaning
SaProt	LLR -7.03	tolerated
⇒ AlphaMissense, REVEL and SaProt all call this tolerated.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 4.1	GERP 1.2, phastCons 1
Regional constraint	o/e 0.85	unconstrained · MANE · 29 kb · p 4.3e-06 · regional, not allelic
Overall
CADD	22.8	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

No allele count reported in gnomAD v4.1 (AN 1,581,336). This is missing data, not an absence: the variant may or may not be present in gnomAD. Rarity (ACMG PM2) and BA1/BS1 cannot be assessed for it.

Variant & gene context

Gene: CAPN1
Protein: p.Ala23Val
Coding: c.68C>T
MANE Select: NM_005186
dbSNP: rs2137305477
Type: single nucleotide variant
Location: chr11:65182769 (GRCh38)
Gene constraint: LOEUF 0.977 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 90.03 · 5 PDB

Full CAPN1 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Similar variants

CAPN1 c.1605+5G>A Pathogenic/Likely pathogenic ★★ same type
CAPN1 c.267+2T>C Pathogenic/Likely pathogenic ★★ same type
CAPN1 c.338-1G>A Pathogenic ★★ same type
CAPN1 c.759+1G>A Pathogenic ★★ same type
CAPN1 c.843+1G>C Pathogenic/Likely pathogenic ★★ same type
CAPN1 c.929+2T>A Likely pathogenic ★★ same type
CAPN1 p.Arg285Ter Pathogenic/Likely pathogenic ★★ same type
CAPN1 p.Arg385Ter Pathogenic/Likely pathogenic ★★ 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/capn1-p-ala23val (accessed [today's date]).

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