Is CAPN5 p.Arg18Trp (c.52C>T) pathogenic?

CAPN5 p.Arg18Trp (c.52C>T) is classified Conflicting classifications of pathogenicity in CAPN5 (ClinVar, Conflicting submitters, 4 submitters; last evaluated 2026-01-06). AlphaMissense: likely benign (0.1801); Rare (popmax 0.176%, afr); Associated with Inborn genetic diseases.

What condition is associated with CAPN5 p.Arg18Trp (c.52C>T)?

CAPN5 p.Arg18Trp (c.52C>T) is associated with Inborn genetic diseases (ClinVar).

How common is CAPN5 p.Arg18Trp (c.52C>T) in the general population?

CAPN5 p.Arg18Trp (c.52C>T) is rare (popmax 0.176%, afr) (gnomAD).

What do computational predictors say about CAPN5 p.Arg18Trp (c.52C>T)?

AlphaMissense predicts likely benign (score 0.1801) — an in-silico prediction, not a clinical call.

CAPN5 p.Arg18Trp

c.52C>T · rs149132399 · VCV501411

Conflicting classifications of pathogenicity Conflicting submitters

Classification

Conflicting classifications of pathogenicity

ClinVar

Review

Conflicting submitters ★☆☆☆

ClinVar · 4 submitters

AlphaMissense

likely benign

0.1801 · ACMG-weighted

gnomAD v4.1

Rare

rare (popmax 0.176%, afr)

Missense predictors

0/2 damaging

AlphaMissense, SaProt · REVEL no call

Conditions

Inborn genetic diseases

Computational evidence

Protein change
AlphaMissense	0.1801	likely benign
REVEL	0.293	indeterminate
SaProt	LLR -9.84	tolerated
⇒ AlphaMissense and SaProt both call this tolerated; REVEL makes no call.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 2.7	GERP 0.46, phastCons 1
Regional constraint	o/e 0.89	unconstrained · MANE · 39 kb · p 0.00098 · regional, not allelic
Overall
CADD	28.0	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 0.176% African / African-American · 132/74,932 alleles

Filtering AF 0.152% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.142%

Overall 0.0203% 327/1,613,774 alleles · rare

Ancestry group	Frequency	1 in
African / African-Americangrpmax	0.176%	568
Remaining individualsnot grpmax-eligible	0.0352%	2,840
Admixed American	0.0283%	3,530
South Asian	0.0253%	3,960
European (non-Finnish)	0.0111%	9,008
East Asian	0.00446%	22,444

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.Arg18Trp
Coding: c.52C>T
MANE Select: NM_004055
dbSNP: rs149132399
Type: single nucleotide variant
Location: chr11:77084938 (GRCh38)
Gene constraint: LOEUF 0.928 · pLI <0.01 · ClinGen HI 0/3 (gnomAD)
Structure: AlphaFold pLDDT 91.71 · 1 PDB
Residue 18: an α-helix

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

Disease context

Inborn genetic diseases — disease report on Sugi Atlas → Associated genes, phenotypes, clinical trials & treatments

Similar variants

CAPN5 p.Arg18Gln Benign/Likely benign ★★ same residue
CAPN5 p.Ala183Ser Uncertain significance ★★ ⚠ same condition
CAPN5 p.Ala237Val Uncertain significance ★★ ⚠ same condition
CAPN5 p.Ala253Thr Uncertain significance ★★ ⚠ same condition
CAPN5 p.Ala34Val Uncertain significance ★★ ⚠ same condition
CAPN5 p.Ala357Val Uncertain significance ★★ ⚠ same condition
CAPN5 p.Ala362Gly Uncertain significance ★★ ⚠ same condition
CAPN5 p.Ala447Thr Uncertain significance ★★ ⚠ same condition

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-arg18trp (accessed [today's date]).

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