Is CAPN13 p.Phe601Leu (c.1803C>A) pathogenic?

CAPN13 p.Phe601Leu (c.1803C>A) is classified Uncertain significance in CAPN13 (ClinVar, Single submitter, 1 submitter; last evaluated 2023-03-17). AlphaMissense: likely pathogenic (0.7314); Very rare (popmax 0.0028%, nfe).

How common is CAPN13 p.Phe601Leu (c.1803C>A) in the general population?

CAPN13 p.Phe601Leu (c.1803C>A) is very rare (popmax 0.0028%, nfe) (gnomAD).

What do computational predictors say about CAPN13 p.Phe601Leu (c.1803C>A)?

AlphaMissense predicts likely pathogenic (score 0.7314) — an in-silico prediction, not a clinical call.

CAPN13 p.Phe601Leu

c.1803C>A · rs772084845 · VCV2523617

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely pathogenic

0.7314 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 0.0028%, nfe)

Missense predictors

1/2 damaging

AlphaMissense, SaProt · REVEL no call

Computational evidence

Protein change
AlphaMissense	0.7314	likely pathogenic · top 8% in CAPN13
REVEL	0.422	indeterminate
SaProt	LLR -4.47	tolerated
⇒ AlphaMissense calls this damaging; SaProt does not; REVEL makes no call.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 3.1	GERP 0.14, phastCons 1
Regional constraint	o/e 1.05	unconstrained · MANE · 57 kb · p 0.12 · regional, not allelic
Overall
CADD	17.01	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 0.0028% European (non-Finnish) · 33/1,177,702 alleles

Filtering AF 0.002% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.00176%

Overall 0.00212% 34/1,607,458 alleles · very rare

Ancestry group	Frequency	1 in
European (non-Finnish)grpmax	0.0028%	35,688
South Asian	0.00111%	89,872

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: CAPN13
Protein: p.Phe601Leu
Coding: c.1803C>A
MANE Select: NM_144575
dbSNP: rs772084845
Type: single nucleotide variant
Location: chr2:30732562 (GRCh38)
Gene constraint: LOEUF 1.121 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 83.25 · 1 PDB
Residue 601: an α-helix

Full CAPN13 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Similar variants

CAPN13 p.Ala172Ser Uncertain significance ★ ⚠ same type
CAPN13 p.Ala215Ser Uncertain significance ★ ⚠ same type
CAPN13 p.Ala2Val Uncertain significance ★ ⚠ same type
CAPN13 p.Ala326Val Uncertain significance ★ ⚠ same type
CAPN13 p.Ala460Gly Uncertain significance ★ ⚠ same type
CAPN13 p.Ala510Pro Uncertain significance ★ ⚠ same type
CAPN13 p.Ala564Val Uncertain significance ★ ⚠ same type
CAPN13 p.Ala90Ser 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/capn13-p-phe601leu (accessed [today's date]).

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