Is CAPN15 p.Ala809Val (c.2426C>T) pathogenic?

CAPN15 p.Ala809Val (c.2426C>T) is classified Uncertain significance in CAPN15 (ClinVar, Single submitter, 1 submitter; last evaluated 2025-12-16). AlphaMissense: ambiguous (0.4932); Very rare (popmax 0.00196%, amr).

How common is CAPN15 p.Ala809Val (c.2426C>T) in the general population?

CAPN15 p.Ala809Val (c.2426C>T) is very rare (popmax 0.00196%, amr) (gnomAD).

What do computational predictors say about CAPN15 p.Ala809Val (c.2426C>T)?

AlphaMissense predicts ambiguous (score 0.4932) — an in-silico prediction, not a clinical call.

CAPN15 p.Ala809Val

c.2426C>T · VCV4829978

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

ambiguous

0.4932 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 0.00196%, amr)

Computational evidence

Protein change
AlphaMissense	0.4932	ambiguous
REVEL	0.461	indeterminate
SaProt	LLR -8.43	tolerated
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 7.6	GERP 1.5, phastCons 1
Regional constraint	o/e 0.92	unconstrained · MANE · 4,055 bp · p 0.036 · regional, not allelic
Overall
CADD	24.2	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 0.00196% Admixed American · 1/50,916 alleles

Overall 0.000215% 3/1,395,698 alleles · very rare

Ancestry group	Frequency	1 in
Admixed Americangrpmax	0.00196%	50,916
Remaining individualsnot grpmax-eligible	0.00167%	59,904
European (non-Finnish)	8.72e-05%	1,146,354

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: CAPN15
Protein: p.Ala809Val
Coding: c.2426C>T
MANE Select: NM_005632
Type: single nucleotide variant
Location: chr16:552131 (GRCh38)
Gene constraint: LOEUF 0.974 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 71.65

Full CAPN15 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Similar variants

CAPN15 c.2192+8C>T Uncertain significance ★★ same type
CAPN15 p.Arg428Trp Uncertain significance ★★ ⚠ same type
CAPN15 p.Arg867Cys Uncertain significance ★★ ⚠ same type
CAPN15 p.Arg867His Uncertain significance ★★ ⚠ same type
CAPN15 p.Cys363Arg Uncertain significance ★★ ⚠ same type
CAPN15 p.Glu776Ala Uncertain significance ★★ ⚠ same type
CAPN15 p.Val489Met Uncertain significance ★★ ⚠ same type
CAPN15 p.Val841Met Uncertain significance ★★ ⚠ 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/capn15-p-ala809val (accessed [today's date]).

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