Is CAPN3 p.Ile806Ser (c.2417T>G) pathogenic?

CAPN3 p.Ile806Ser (c.2417T>G) is classified Uncertain significance in CAPN3 (ClinVar, Single submitter, 1 submitter; last evaluated 2022-05-03). AlphaMissense: ambiguous (0.4275); Very rare (popmax 0.000508%, nfe).

How common is CAPN3 p.Ile806Ser (c.2417T>G) in the general population?

CAPN3 p.Ile806Ser (c.2417T>G) is very rare (popmax 0.000508%, nfe) (gnomAD).

What do computational predictors say about CAPN3 p.Ile806Ser (c.2417T>G)?

AlphaMissense predicts ambiguous (score 0.4275) — an in-silico prediction, not a clinical call.

CAPN3 p.Ile806Ser

c.2417T>G · rs753854306 · VCV1696072

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

ambiguous

0.4275 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 0.000508%, nfe)

Computational evidence

Protein change
AlphaMissense	0.4275	ambiguous
REVEL	0.468	indeterminate
SaProt	LLR -9.11	tolerated
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 5.1	GERP 2.9, phastCons 1
Regional constraint	o/e 0.96	unconstrained · MANE · 52 kb · p 0.21 · regional, not allelic
Overall
CADD	24.1	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 0.000508% European (non-Finnish) · 6/1,180,004 alleles

Filtering AF 0.000183% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.00012%

Overall 0.000372% 6/1,614,002 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: CAPN3
Protein: p.Ile806Ser
Coding: c.2417T>G
MANE Select: NM_000070
dbSNP: rs753854306
Type: single nucleotide variant
Location: chr15:42411323 (GRCh38)
Gene constraint: LOEUF 0.896 · pLI <0.01 · ClinGen HI gene assoc. with recessive phenotype (gnomAD)
Structure: AlphaFold pLDDT 79.18 · 5 PDB
Residue 806: the 'domain iv' region; a β-strand; a binding site; the ef-hand 4 domain

Full CAPN3 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Similar variants

CAPN3 c.1115+5G>C Pathogenic ★★★ same type
CAPN3 c.1194-2A>G Pathogenic ★★★ same type
CAPN3 c.1194-9A>G Pathogenic ★★★ same type
CAPN3 c.1746-20C>G Pathogenic ★★★ same type
CAPN3 c.1993-1G>A Pathogenic ★★★ same type
CAPN3 c.499-1G>A Pathogenic ★★★ same type
CAPN3 p.Ala702Val Pathogenic ★★★ same type
CAPN3 p.Ala798Glu Pathogenic ★★★ ⚠ 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/capn3-p-ile806ser (accessed [today's date]).

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