Is CAPN10 p.Ala389= (c.1167G>A) pathogenic?

CAPN10 p.Ala389= (c.1167G>A) is classified Likely benign in CAPN10 (ClinVar, Single submitter, 1 submitter; last evaluated 2025-08-23). Rare (popmax 0.103%, eas); Associated with Inborn genetic diseases.

What condition is associated with CAPN10 p.Ala389= (c.1167G>A)?

CAPN10 p.Ala389= (c.1167G>A) is associated with Inborn genetic diseases (ClinVar).

How common is CAPN10 p.Ala389= (c.1167G>A) in the general population?

CAPN10 p.Ala389= (c.1167G>A) is rare (popmax 0.103%, eas) (gnomAD).

CAPN10 p.Ala389=

c.1167G>A · VCV4218743

Likely benign Single submitter

Classification

Likely benign

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

gnomAD v4.1

Rare

rare (popmax 0.103%, eas)

Conditions

Inborn genetic diseases

Computational evidence

Protein change
Missense predictors do not apply to this variant type; conservation carries the signal.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP -0.87	GERP -1.9
Overall
CADD	0.695	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.103% East Asian · 46/44,872 alleles

Filtering AF 0.0789% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.0706%

Overall 0.00372% 60/1,613,760 alleles · rare

Ancestry group	Frequency	1 in
East Asiangrpmax	0.103%	975
Remaining individualsnot grpmax-eligible	0.0048%	20,834
Admixed American	0.00333%	30,012
African / African-American	0.00266%	37,527
European (non-Finnish)	0.000593%	168,573

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: CAPN10
Protein: p.Ala389=
Coding: c.1167G>A
MANE Select: NM_023083
Type: single nucleotide variant
Location: chr2:240595193 (GRCh38)
Gene constraint: LOEUF 1.121 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 83.91
Residue 389: the 'domain iii 1' region

Full CAPN10 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

CAPN10 p.Ala389Val Uncertain significance ★ ⚠ same residue
CAPN10 p.Arg127Cys Uncertain significance ★★ ⚠ same condition
CAPN10 p.Gly526Ser Uncertain significance ★★ ⚠ same condition
CAPN10 p.Pro46Ser Uncertain significance ★★ ⚠ same condition
CAPN10 p.Thr339Met Uncertain significance ★★ ⚠ same condition
CAPN10 p.Ala156Thr Uncertain significance ★ ⚠ same condition
CAPN10 p.Ala252Val Uncertain significance ★ ⚠ same condition
CAPN10 p.Ala341Thr 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/capn10-p-ala389 (accessed [today's date]).

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