Is CAPN1 p.Arg567Trp (c.1699C>T) pathogenic?

CAPN1 p.Arg567Trp (c.1699C>T) is classified Uncertain significance in CAPN1 (ClinVar, Single submitter, 1 submitter; last evaluated 2022-02-19). AlphaMissense: ambiguous (0.4033); Ultra-rare (popmax 0.0222%, nfe).

How common is CAPN1 p.Arg567Trp (c.1699C>T) in the general population?

CAPN1 p.Arg567Trp (c.1699C>T) is ultra-rare (popmax 0.0222%, nfe) (gnomAD).

What do computational predictors say about CAPN1 p.Arg567Trp (c.1699C>T)?

AlphaMissense predicts ambiguous (score 0.4033) — an in-silico prediction, not a clinical call.

CAPN1 p.Arg567Trp

c.1699C>T · rs200944311 · VCV2056799

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

ambiguous

0.4033 · ACMG-weighted

gnomAD v4.1

Rare

ultra-rare (popmax 0.0222%, nfe)

Computational evidence

Protein change
AlphaMissense	0.4033	ambiguous
REVEL	0.459	indeterminate
SaProt	LLR -12.53	damaging
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 4.6	GERP 0.72, phastCons 0.45
Regional constraint	o/e 0.85	unconstrained · MANE · 29 kb · p 4.3e-06 · regional, not allelic
Overall
CADD	26.8	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 0.0222% European (non-Finnish) · 258/1,159,582 alleles

Filtering AF 0.02% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.0191%

Overall 0.0185% 291/1,573,966 alleles · ultra-rare

Ancestry group	Frequency	1 in
European (non-Finnish)grpmax	0.0222%	4,495
Middle Eastern	0.0166%	6,016
Remaining individualsnot grpmax-eligible	0.0164%	6,105
South Asian	0.0128%	7,791
Admixed American	0.0093%	10,752
Finnishnot grpmax-eligible	0.00652%	15,345
African / African-American	0.0027%	37,031

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: CAPN1
Protein: p.Arg567Trp
Coding: c.1699C>T
MANE Select: NM_005186
dbSNP: rs200944311
Type: single nucleotide variant
Location: chr11:65208232 (GRCh38)
Gene constraint: LOEUF 0.977 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 90.03 · 5 PDB
Residue 567: the ef-hand 1 domain; the 'domain iv' region

Full CAPN1 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Similar variants

CAPN1 p.Arg567Gln Conflicting classifications of pathogenicity ★ ⚠ same residue
CAPN1 c.1605+5G>A Pathogenic/Likely pathogenic ★★ same type
CAPN1 c.267+2T>C Pathogenic/Likely pathogenic ★★ same type
CAPN1 c.338-1G>A Pathogenic ★★ same type
CAPN1 c.759+1G>A Pathogenic ★★ same type
CAPN1 c.843+1G>C Pathogenic/Likely pathogenic ★★ same type
CAPN1 c.929+2T>A Likely pathogenic ★★ same type
CAPN1 p.Arg285Ter Pathogenic/Likely 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/capn1-p-arg567trp (accessed [today's date]).

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