Is CAPN7 p.Phe468Leu (c.1404C>G) pathogenic?

CAPN7 p.Phe468Leu (c.1404C>G) is classified Uncertain significance in CAPN7 (ClinVar, Single submitter, 1 submitter; last evaluated 2023-09-29). AlphaMissense: likely pathogenic (0.7285); Absent from gnomAD v4.1.

How common is CAPN7 p.Phe468Leu (c.1404C>G) in the general population?

CAPN7 p.Phe468Leu (c.1404C>G) is absent from gnomAD v4.1 (gnomAD).

What do computational predictors say about CAPN7 p.Phe468Leu (c.1404C>G)?

AlphaMissense predicts likely pathogenic (score 0.7285) — an in-silico prediction, not a clinical call.

CAPN7 p.Phe468Leu

c.1404C>G · rs748798137 · VCV3137176

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely pathogenic

0.7285 · ACMG-weighted

gnomAD v4.1

Absent

absent from gnomAD v4.1

Missense predictors

1/3 damaging

AlphaMissense, REVEL, SaProt

Computational evidence

Protein change
AlphaMissense	0.7285	likely pathogenic
REVEL	0.178	moderately benign-leaning
SaProt	LLR -8.49	tolerated
⇒ AlphaMissense calls this damaging; REVEL and SaProt do not.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 0.58	GERP 0.88, phastCons 1
Regional constraint	o/e 0.88	unconstrained · MANE · 28 kb · p 0.0017 · regional, not allelic
Overall
CADD	17.66	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

Absent from gnomAD v4.1. Not observed in any sequenced alleles — a rarity signal (ACMG PM2-supporting), not evidence of pathogenicity on its own.

Variant & gene context

Gene: CAPN7
Protein: p.Phe468Leu
Coding: c.1404C>G
MANE Select: NM_014296
dbSNP: rs748798137
Type: single nucleotide variant
Location: chr3:15235142 (GRCh38)
Gene constraint: LOEUF 0.882 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 88.88 · 2 PDB
Residue 468: the calpain catalytic domain

Full CAPN7 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Similar variants

CAPN7 c.2073+1G>T Uncertain significance ★ same type
CAPN7 p.Ala10Asp Uncertain significance ★ ⚠ same type
CAPN7 p.Ala10Ser Uncertain significance ★ ⚠ same type
CAPN7 p.Ala149Val Uncertain significance ★ ⚠ same type
CAPN7 p.Ala29Val Uncertain significance ★ ⚠ same type
CAPN7 p.Ala37Thr Uncertain significance ★ ⚠ same type
CAPN7 p.Ala39Asp Uncertain significance ★ ⚠ same type
CAPN7 p.Ala459Ser 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/capn7-p-phe468leu (accessed [today's date]).

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