Is CAPN7 p.Ala39Asp (c.116C>A) pathogenic?

CAPN7 p.Ala39Asp (c.116C>A) is classified Uncertain significance in CAPN7 (ClinVar, Single submitter, 1 submitter; last evaluated 2022-11-18). AlphaMissense: likely pathogenic (0.9927); Very rare (popmax 0.00111%, nfe).

How common is CAPN7 p.Ala39Asp (c.116C>A) in the general population?

CAPN7 p.Ala39Asp (c.116C>A) is very rare (popmax 0.00111%, nfe) (gnomAD).

What do computational predictors say about CAPN7 p.Ala39Asp (c.116C>A)?

AlphaMissense predicts likely pathogenic (score 0.9927) — an in-silico prediction, not a clinical call.

CAPN7 p.Ala39Asp

c.116C>A · rs748864995 · VCV2327968

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely pathogenic

0.9927 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 0.00111%, nfe)

Missense predictors

1/2 damaging

AlphaMissense, SaProt · REVEL no call

Computational evidence

Protein change
AlphaMissense	0.9927	likely pathogenic
REVEL	0.6	indeterminate
SaProt	LLR -9.22	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 7.6	GERP 1.6, 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 0.00111% European (non-Finnish) · 13/1,175,192 alleles

Filtering AF 0.000617% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.000476%

Overall 0.00081% 13/1,604,700 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.Ala39Asp
Coding: c.116C>A
MANE Select: NM_014296
dbSNP: rs748864995
Type: single nucleotide variant
Location: chr3:15212117 (GRCh38)
Gene constraint: LOEUF 0.882 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 88.88 · 2 PDB
Residue 39: 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.Ala459Ser Uncertain significance ★ ⚠ same type
CAPN7 p.Ala583Thr 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-ala39asp (accessed [today's date]).

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