Is CAPN7 p.Ser27Cys (c.80C>G) pathogenic?

CAPN7 p.Ser27Cys (c.80C>G) is classified Uncertain significance in CAPN7 (ClinVar, Single submitter, 1 submitter; last evaluated 2024-11-26). AlphaMissense: likely benign (0.1021); Ultra-rare (popmax 0.0707%, nfe).

How common is CAPN7 p.Ser27Cys (c.80C>G) in the general population?

CAPN7 p.Ser27Cys (c.80C>G) is ultra-rare (popmax 0.0707%, nfe) (gnomAD).

What do computational predictors say about CAPN7 p.Ser27Cys (c.80C>G)?

AlphaMissense predicts likely benign (score 0.1021) — an in-silico prediction, not a clinical call.

CAPN7 p.Ser27Cys

c.80C>G · rs199777131 · VCV2355195

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.1021 · ACMG-weighted

gnomAD v4.1

Rare

ultra-rare (popmax 0.0707%, nfe)

Missense predictors

1/3 damaging

AlphaMissense, REVEL, SaProt

Computational evidence

Protein change
AlphaMissense	0.1021	likely benign
REVEL	0.231	benign-leaning
SaProt	LLR -10.16	damaging
⇒ SaProt calls this damaging; AlphaMissense and REVEL do not.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 3	GERP 0.18, phastCons 0.43
Regional constraint	o/e 1.13	unconstrained · MANE · 14 kb · p 0.042 · regional, not allelic
Overall
CADD	23.9	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 0.0707% European (non-Finnish) · 811/1,147,474 alleles

Filtering AF 0.0666% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.065%

Overall 0.0557% 864/1,551,022 alleles · ultra-rare

Ancestry group	Frequency	1 in
European (non-Finnish)grpmax	0.0707%	1,415
Remaining individualsnot grpmax-eligible	0.0516%	1,938
Admixed American	0.0235%	4,258
Middle Eastern	0.0172%	5,812
African / African-American	0.00827%	12,095
Ashkenazi Jewishnot grpmax-eligible	0.00351%	28,508
Finnishnot grpmax-eligible	0.00335%	29,827

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.Ser27Cys
Coding: c.80C>G
MANE Select: NM_014296
dbSNP: rs199777131
Type: single nucleotide variant
Location: chr3:15206575 (GRCh38)
Gene constraint: LOEUF 0.882 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 88.88 · 2 PDB
Residue 27: 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-ser27cys (accessed [today's date]).

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