Is CAPN7 p.Glu7Gln (c.19G>C) pathogenic?

CAPN7 p.Glu7Gln (c.19G>C) is classified Uncertain significance in CAPN7 (ClinVar, Single submitter, 1 submitter; last evaluated 2021-08-06). AlphaMissense: ambiguous (0.3838); Very rare (popmax 8.71e-05%, nfe).

How common is CAPN7 p.Glu7Gln (c.19G>C) in the general population?

CAPN7 p.Glu7Gln (c.19G>C) is very rare (popmax 8.71e-05%, nfe) (gnomAD).

What do computational predictors say about CAPN7 p.Glu7Gln (c.19G>C)?

AlphaMissense predicts ambiguous (score 0.3838) — an in-silico prediction, not a clinical call.

CAPN7 p.Glu7Gln

c.19G>C · rs1316702465 · VCV2233708

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

ambiguous

0.3838 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 8.71e-05%, nfe)

Missense predictors

0/2 damaging

REVEL, SaProt · AlphaMissense no call

Computational evidence

Protein change
AlphaMissense	0.3838	ambiguous
REVEL	0.207	benign-leaning
SaProt	LLR -6.93	tolerated
⇒ REVEL and SaProt both call this tolerated; AlphaMissense makes no call.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 9.1	GERP 1.1, phastCons 1
Regional constraint	o/e 1.13	unconstrained · MANE · 14 kb · p 0.042 · regional, not allelic
Overall
CADD	25.1	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 8.71e-05% European (non-Finnish) · 1/1,148,718 alleles

Overall 7.14e-05% 1/1,400,498 alleles · very rare

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.Glu7Gln
Coding: c.19G>C
MANE Select: NM_014296
dbSNP: rs1316702465
Type: single nucleotide variant
Location: chr3:15206514 (GRCh38)
Gene constraint: LOEUF 0.882 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 88.88 · 2 PDB
Residue 7: an α-helix

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-glu7gln (accessed [today's date]).

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