Is CAPN7 p.His458= (c.1374C>T) pathogenic?

CAPN7 p.His458= (c.1374C>T) is classified Likely benign in CAPN7 (ClinVar, Single submitter, 1 submitter; last evaluated 2025-10-01). Very rare (popmax 0.00958%, nfe).

How common is CAPN7 p.His458= (c.1374C>T) in the general population?

CAPN7 p.His458= (c.1374C>T) is very rare (popmax 0.00958%, nfe) (gnomAD).

CAPN7 p.His458=

c.1374C>T · VCV4534205

Likely benign Single submitter

Classification

Likely benign

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

gnomAD v4.1

Rare

very rare (popmax 0.00958%, nfe)

Computational evidence

Protein change
Missense predictors do not apply to this variant type; conservation carries the signal.
REVEL	0.49	indeterminate
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP -4	GERP -3.5
Overall
CADD	4.779	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.00958% European (non-Finnish) · 113/1,179,464 alleles

Filtering AF 0.0081% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.0076%

Overall 0.00738% 119/1,612,858 alleles · very rare

Ancestry group	Frequency	1 in
European (non-Finnish)grpmax	0.00958%	10,438
Remaining individualsnot grpmax-eligible	0.00481%	20,810
East Asian	0.00223%	44,870
Admixed American	0.00167%	59,772
South Asian	0.0011%	90,926

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: CAPN7
Protein: p.His458=
Coding: c.1374C>T
MANE Select: NM_014296
Type: single nucleotide variant
Location: chr3:15235112 (GRCh38)
Gene constraint: LOEUF 0.882 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 88.88 · 2 PDB
Residue 458: the calpain catalytic domain; an active site

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-his458 (accessed [today's date]).

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