Is CAPN15 p.Val1077= (c.3231C>T) pathogenic?

CAPN15 p.Val1077= (c.3231C>T) is classified Likely benign in CAPN15 (ClinVar, No assertion criteria, 1 submitter; last evaluated 2019-08-19). Ultra-rare (popmax 0.0157%, eas); Associated with CAPN15-related disorder.

What condition is associated with CAPN15 p.Val1077= (c.3231C>T)?

CAPN15 p.Val1077= (c.3231C>T) is associated with CAPN15-related disorder (ClinVar).

How common is CAPN15 p.Val1077= (c.3231C>T) in the general population?

CAPN15 p.Val1077= (c.3231C>T) is ultra-rare (popmax 0.0157%, eas) (gnomAD).

CAPN15 p.Val1077=

c.3231C>T · rs374037837 · VCV3052759

Likely benign No assertion criteria

Classification

Likely benign

ClinVar

Review

No assertion criteria ☆☆☆☆

ClinVar · 1 submitter

gnomAD v4.1

Rare

ultra-rare (popmax 0.0157%, eas)

Conditions

CAPN15-related disorder

Computational evidence

Protein change
Missense predictors do not apply to this variant type; conservation carries the signal.
Splicing
SpliceAI	<0.2	all four deltas below 0.2 · C>A here scores Δ0.21 · evaluated, not missing
Constraint at this position
Conservation	phyloP -8	GERP -2.8
Overall
CADD	0.109	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.0157% East Asian · 7/44,662 alleles

Filtering AF 0.00729% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.00617%

Overall 0.00696% 112/1,610,298 alleles · ultra-rare

Ancestry group	Frequency	1 in
East Asiangrpmax	0.0157%	6,380
Remaining individualsnot grpmax-eligible	0.0128%	7,797
European (non-Finnish)	0.00797%	12,539
African / African-American	0.00267%	37,399
South Asian	0.0011%	90,882

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.Val1077=
Coding: c.3231C>T
MANE Select: NM_005632
dbSNP: rs374037837
Type: single nucleotide variant
Location: chr16:553486 (GRCh38)
Gene constraint: LOEUF 0.974 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 71.65
Residue 1077: the 'disordered' region

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

Disease context

CAPN15-related disorder

Similar variants

CAPN15 p.Pro494Ser Uncertain significance ★ ⚠ same condition
CAPN15 p.Ser613Leu Conflicting classifications of pathogenicity ★ ⚠ same condition
CAPN15 p.Thr950Ala Uncertain significance ⚠ same condition
CAPN15 p.Ala559= Likely benign same condition
CAPN15 p.Ala817= Likely benign same condition
CAPN15 p.Arg428Gln Likely benign same condition
CAPN15 p.Asn745= Likely benign same condition
CAPN15 p.Asp590= Benign 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/capn15-p-val1077 (accessed [today's date]).

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