Is CAPN5 p.Ala34Val (c.101C>T) pathogenic?

CAPN5 p.Ala34Val (c.101C>T) is classified Uncertain significance in CAPN5 (ClinVar, Multiple submitters, 2 submitters; last evaluated 2025-08-13). AlphaMissense: ambiguous (0.437); Very rare (popmax 0.00881%, nfe); Associated with Inborn genetic diseases.

What condition is associated with CAPN5 p.Ala34Val (c.101C>T)?

CAPN5 p.Ala34Val (c.101C>T) is associated with Inborn genetic diseases (ClinVar).

How common is CAPN5 p.Ala34Val (c.101C>T) in the general population?

CAPN5 p.Ala34Val (c.101C>T) is very rare (popmax 0.00881%, nfe) (gnomAD).

What do computational predictors say about CAPN5 p.Ala34Val (c.101C>T)?

AlphaMissense predicts ambiguous (score 0.437) — an in-silico prediction, not a clinical call.

CAPN5 p.Ala34Val

c.101C>T · rs782469382 · VCV848814

Uncertain significance Multiple submitters

Classification

Uncertain significance

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 2 submitters

AlphaMissense

ambiguous

0.437 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 0.00881%, nfe)

Conditions

Inborn genetic diseases

Computational evidence

Protein change
AlphaMissense	0.437	ambiguous
REVEL	0.331	indeterminate
SaProt	LLR -9.02	tolerated
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 7.6	GERP 1.6, phastCons 1
Regional constraint	o/e 0.89	unconstrained · MANE · 39 kb · p 0.00098 · regional, not allelic
Overall
CADD	24.7	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 0.00881% European (non-Finnish) · 104/1,180,046 alleles

Filtering AF 0.00741% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.00692%

Overall 0.00682% 110/1,613,786 alleles · very rare

Ancestry group	Frequency	1 in
European (non-Finnish)grpmax	0.00881%	11,347
South Asian	0.00439%	22,773
Ashkenazi Jewishnot grpmax-eligible	0.00338%	29,608
Remaining individualsnot grpmax-eligible	0.0016%	62,486

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.Ala34Val
Coding: c.101C>T
MANE Select: NM_004055
dbSNP: rs782469382
Type: single nucleotide variant
Location: chr11:77084987 (GRCh38)
Gene constraint: LOEUF 0.928 · pLI <0.01 · ClinGen HI 0/3 (gnomAD)
Structure: AlphaFold pLDDT 91.71 · 1 PDB
Residue 34: the calpain catalytic domain

Full CAPN5 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

CAPN5 p.Ala34= Likely benign ★★ same residue
CAPN5 p.Ala34Thr Conflicting classifications of pathogenicity ★ ⚠ same residue
CAPN5 p.Ala183Ser Uncertain significance ★★ ⚠ same condition
CAPN5 p.Ala237Val Uncertain significance ★★ ⚠ same condition
CAPN5 p.Ala253Thr Uncertain significance ★★ ⚠ same condition
CAPN5 p.Ala357Val Uncertain significance ★★ ⚠ same condition
CAPN5 p.Ala362Gly Uncertain significance ★★ ⚠ same condition
CAPN5 p.Ala447Thr 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/capn5-p-ala34val (accessed [today's date]).

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