Is CAPN7 p.Ile804Ser (c.2411T>G) pathogenic?

CAPN7 p.Ile804Ser (c.2411T>G) is classified Uncertain significance in CAPN7 (ClinVar, Single submitter, 1 submitter; last evaluated 2025-05-16). AlphaMissense: likely benign (0.0651); Ultra-rare (popmax 0.0113%, sas).

How common is CAPN7 p.Ile804Ser (c.2411T>G) in the general population?

CAPN7 p.Ile804Ser (c.2411T>G) is ultra-rare (popmax 0.0113%, sas) (gnomAD).

What do computational predictors say about CAPN7 p.Ile804Ser (c.2411T>G)?

AlphaMissense predicts likely benign (score 0.0651) — an in-silico prediction, not a clinical call.

CAPN7 p.Ile804Ser

c.2411T>G · VCV3995263

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.0651 · ACMG-weighted

gnomAD v4.1

Rare

ultra-rare (popmax 0.0113%, sas)

Missense predictors

0/3 damaging

AlphaMissense, REVEL, SaProt

Computational evidence

Protein change
AlphaMissense	0.0651	likely benign
REVEL	0.274	benign-leaning
SaProt	LLR -0.90	tolerated
⇒ AlphaMissense, REVEL and SaProt all call this tolerated.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 0.45	GERP -3.9
Regional constraint	o/e 0.88	unconstrained · MANE · 28 kb · p 0.0017 · regional, not allelic
Overall
CADD	5.944	PHRED · no single calibrated threshold — expert panels disagree

ClinVar classifies this uncertain; the computational predictors unanimously lean tolerated — a triage signal, not a reclassification

AlphaMissense carries the ACMG weight for missense; REVEL and SaProt are independent agreement signals.

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.0113% South Asian · 10/88,722 alleles

Filtering AF 0.00608% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.00464%

Overall 0.000964% 14/1,452,512 alleles · ultra-rare

Ancestry group	Frequency	1 in
South Asiangrpmax	0.0113%	8,872
Admixed American	0.00174%	57,418
Remaining individualsnot grpmax-eligible	0.00161%	62,084
European (non-Finnish)	0.00017%	588,696

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.Ile804Ser
Coding: c.2411T>G
MANE Select: NM_014296
Type: single nucleotide variant
Location: chr3:15251229 (GRCh38)
Gene constraint: LOEUF 0.882 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 88.88 · 2 PDB
Residue 804: a β-strand; the 'domain n' region

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-ile804ser (accessed [today's date]).

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