Is CAPN15 p.Ala799Val (c.2396C>T) pathogenic?

CAPN15 p.Ala799Val (c.2396C>T) is classified Likely benign in CAPN15 (ClinVar, Single submitter, 1 submitter; last evaluated 2025-01-02). AlphaMissense: likely benign (0.0623); Ultra-rare (popmax 0.0171%, eas).

How common is CAPN15 p.Ala799Val (c.2396C>T) in the general population?

CAPN15 p.Ala799Val (c.2396C>T) is ultra-rare (popmax 0.0171%, eas) (gnomAD).

What do computational predictors say about CAPN15 p.Ala799Val (c.2396C>T)?

AlphaMissense predicts likely benign (score 0.0623) — an in-silico prediction, not a clinical call.

CAPN15 p.Ala799Val

c.2396C>T · VCV3827249

Likely benign Single submitter

Classification

Likely benign

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.0623 · ACMG-weighted

gnomAD v4.1

Rare

ultra-rare (popmax 0.0171%, eas)

Missense predictors

0/3 damaging

AlphaMissense, REVEL, SaProt

Computational evidence

Protein change
AlphaMissense	0.0623	likely benign
REVEL	0.101	moderately benign-leaning
SaProt	LLR -5.33	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 0.45	GERP -3, phastCons 0.089
Regional constraint	o/e 0.92	unconstrained · MANE · 4,055 bp · p 0.036 · regional, not allelic
Overall
CADD	6.879	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 0.0171% East Asian · 7/40,942 alleles

Filtering AF 0.00944% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.00739%

Overall 0.00768% 119/1,548,934 alleles · ultra-rare

Ancestry group	Frequency	1 in
East Asiangrpmax	0.0171%	5,849
African / African-American	0.0164%	6,084
South Asian	0.0119%	8,405
European (non-Finnish)	0.00741%	13,493
Ashkenazi Jewishnot grpmax-eligible	0.00699%	14,313
Admixed American	0.00588%	17,009

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.Ala799Val
Coding: c.2396C>T
MANE Select: NM_005632
Type: single nucleotide variant
Location: chr16:552101 (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

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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
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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-ala799val (accessed [today's date]).

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