Is CAPN5 p.Arg18Gln (c.53G>A) pathogenic?

CAPN5 p.Arg18Gln (c.53G>A) is classified Benign/Likely benign in CAPN5 (ClinVar, Multiple submitters, 2 submitters; last evaluated 2025-10-06). AlphaMissense: likely benign (0.0945); Low-frequency (popmax 1.13%, sas).

How common is CAPN5 p.Arg18Gln (c.53G>A) in the general population?

CAPN5 p.Arg18Gln (c.53G>A) is low-frequency (popmax 1.13%, sas) (gnomAD).

What do computational predictors say about CAPN5 p.Arg18Gln (c.53G>A)?

AlphaMissense predicts likely benign (score 0.0945) — an in-silico prediction, not a clinical call.

CAPN5 p.Arg18Gln

c.53G>A · rs200227062 · VCV1167001

Benign/Likely benign Multiple submitters

Classification

Benign/Likely benign

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 2 submitters

AlphaMissense

likely benign

0.0945 · ACMG-weighted

gnomAD v4.1

Rare

low-frequency (popmax 1.13%, sas)

Missense predictors

0/3 damaging

AlphaMissense, REVEL, SaProt

Computational evidence

Protein change
AlphaMissense	0.0945	likely benign
REVEL	0.083	moderately benign-leaning
SaProt	LLR -6.42	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 6.4	GERP 1.6, phastCons 1
Regional constraint	o/e 0.89	unconstrained · MANE · 39 kb · p 0.00098 · regional, not allelic
Overall
CADD	21.3	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 1.13% South Asian · 1,028/91,086 alleles

Filtering AF 1.07% ClinGen BA1/BS1 input FAF95, joint · FAF99 1.05%

Overall 0.0806% 1,301/1,613,954 alleles · low-frequency

Ancestry group	Frequency	1 in
South Asiangrpmax	1.13%	89
Ashkenazi Jewishnot grpmax-eligible	0.284%	352
Middle Eastern	0.0825%	1,212
Remaining individualsnot grpmax-eligible	0.072%	1,389
European (non-Finnish)	0.0114%	8,806
East Asian	0.00446%	22,437
African / African-American	0.00266%	37,535
Admixed American	0.00167%	60,030

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.Arg18Gln
Coding: c.53G>A
MANE Select: NM_004055
dbSNP: rs200227062
Type: single nucleotide variant
Location: chr11:77084939 (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

Similar variants

CAPN5 p.Arg18Trp Conflicting classifications of pathogenicity ★ ⚠ 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
CAPN5 p.Ala245Val 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-arg18gln (accessed [today's date]).

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