Is CAPN15 p.Leu368Pro (c.1103T>C) pathogenic?

CAPN15 p.Leu368Pro (c.1103T>C) is classified Uncertain significance in CAPN15 (ClinVar, Single submitter, 1 submitter; last evaluated 2024-01-12). AlphaMissense: ambiguous (0.4583); Absent from gnomAD v4.1.

How common is CAPN15 p.Leu368Pro (c.1103T>C) in the general population?

CAPN15 p.Leu368Pro (c.1103T>C) is absent from gnomAD v4.1 (gnomAD).

What do computational predictors say about CAPN15 p.Leu368Pro (c.1103T>C)?

AlphaMissense predicts ambiguous (score 0.4583) — an in-silico prediction, not a clinical call.

CAPN15 p.Leu368Pro

c.1103T>C · rs755212538 · VCV3137108

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

ambiguous

0.4583 · ACMG-weighted

gnomAD v4.1

Not reported

no allele count reported in gnomAD v4.1 (AN 1,600,912)

Computational evidence

Protein change
AlphaMissense	0.4583	ambiguous
REVEL	0.584	indeterminate
SaProt	LLR -3.53	tolerated
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 7.8	GERP 1.2, phastCons 1
Regional constraint	o/e 1.14	unconstrained · MANE · 2,296 bp · p 0.00013 · 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

No allele count reported in gnomAD v4.1 (AN 1,600,912). This is missing data, not an absence: the variant may or may not be present in gnomAD. Rarity (ACMG PM2) and BA1/BS1 cannot be assessed for it.

Variant & gene context

Gene: CAPN15
Protein: p.Leu368Pro
Coding: c.1103T>C
MANE Select: NM_005632
dbSNP: rs755212538
Type: single nucleotide variant
Location: chr16:547941 (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-leu368pro (accessed [today's date]).

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