Is CAPN5 p.Arg613Trp (c.1837C>T) pathogenic?

CAPN5 p.Arg613Trp (c.1837C>T) is classified Likely benign in CAPN5 (ClinVar, Multiple submitters, 3 submitters; last evaluated 2025-12-17). AlphaMissense: likely benign (0.0846); Rare (popmax 0.256%, afr).

How common is CAPN5 p.Arg613Trp (c.1837C>T) in the general population?

CAPN5 p.Arg613Trp (c.1837C>T) is rare (popmax 0.256%, afr) (gnomAD).

What do computational predictors say about CAPN5 p.Arg613Trp (c.1837C>T)?

AlphaMissense predicts likely benign (score 0.0846) — an in-silico prediction, not a clinical call.

CAPN5 p.Arg613Trp

c.1837C>T · rs114632044 · VCV1103338

Likely benign Multiple submitters

Classification

Likely benign

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 3 submitters

AlphaMissense

likely benign

0.0846 · ACMG-weighted

gnomAD v4.1

Rare

rare (popmax 0.256%, afr)

Missense predictors

1/3 damaging

AlphaMissense, REVEL, SaProt

Computational evidence

Protein change
AlphaMissense	0.0846	likely benign
REVEL	0.234	benign-leaning
SaProt	LLR -10.46	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 6	GERP 1.9, phastCons 0.98
Regional constraint	o/e 0.89	unconstrained · MANE · 39 kb · p 0.00098 · regional, not allelic
Overall
CADD	26.9	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 0.256% African / African-American · 192/75,038 alleles

Filtering AF 0.226% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.215%

Overall 0.0171% 276/1,613,990 alleles · rare

Ancestry group	Frequency	1 in
African / African-Americangrpmax	0.256%	391
South Asian	0.0373%	2,678
Admixed American	0.0183%	5,455
Middle Eastern	0.0165%	6,060
Remaining individualsnot grpmax-eligible	0.016%	6,250
European (non-Finnish)	0.00237%	42,143

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: CAPN5
Protein: p.Arg613Trp
Coding: c.1837C>T
MANE Select: NM_004055
dbSNP: rs114632044
Type: single nucleotide variant
Location: chr11:77123784 (GRCh38)
Gene constraint: LOEUF 0.928 · pLI <0.01 · ClinGen HI 0/3 (gnomAD)
Structure: AlphaFold pLDDT 91.71 · 1 PDB
Residue 613: the c2 domain

Full CAPN5 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Similar variants

CAPN5 p.Arg613Gln Conflicting classifications of pathogenicity ★ ⚠ same residue
CAPN5 p.Arg613Gly Uncertain significance ★ ⚠ same residue
CAPN5 p.Arg243Leu Pathogenic ★★ same type
CAPN5 p.Arg289Trp Pathogenic ★★ ⚠ same type
CAPN5 p.Ala118Val Uncertain significance ★★ ⚠ same type
CAPN5 p.Ala183Ser Uncertain significance ★★ ⚠ same type
CAPN5 p.Ala185Val Uncertain significance ★★ ⚠ same type
CAPN5 p.Ala237Val 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/capn5-p-arg613trp (accessed [today's date]).

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