Is CAPN5 p.Arg62His (c.185G>A) pathogenic?

CAPN5 p.Arg62His (c.185G>A) is classified Uncertain significance in CAPN5 (ClinVar, Multiple submitters, 4 submitters; last evaluated 2025-10-29). AlphaMissense: likely benign (0.0652); Very rare (popmax 0.00846%, amr); Associated with Inborn genetic diseases.

What condition is associated with CAPN5 p.Arg62His (c.185G>A)?

CAPN5 p.Arg62His (c.185G>A) is associated with Inborn genetic diseases, inherited retinal dystrophy (ClinVar).

How common is CAPN5 p.Arg62His (c.185G>A) in the general population?

CAPN5 p.Arg62His (c.185G>A) is very rare (popmax 0.00846%, amr) (gnomAD).

What do computational predictors say about CAPN5 p.Arg62His (c.185G>A)?

AlphaMissense predicts likely benign (score 0.0652) — an in-silico prediction, not a clinical call.

CAPN5 p.Arg62His

c.185G>A · rs199504989 · VCV971258

Uncertain significance Multiple submitters

Classification

Uncertain significance

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 4 submitters

AlphaMissense

likely benign

0.0652 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 0.00846%, amr)

Missense predictors

0/3 damaging

AlphaMissense, REVEL, SaProt

Conditions

Inborn genetic diseases

Computational evidence

Protein change
AlphaMissense	0.0652	likely benign
REVEL	0.248	benign-leaning
SaProt	LLR -4.98	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 0.57	GERP 1.8, phastCons 0.37
Regional constraint	o/e 0.89	unconstrained · MANE · 39 kb · p 0.00098 · regional, not allelic
Overall
CADD	17.24	PHRED · no single calibrated threshold — expert panels disagree

ClinVar classifies this uncertain; the computational predictors unanimously lean tolerated — a triage signal, not a reclassification

AlphaMissense carries the ACMG weight for missense; REVEL and SaProt are independent agreement signals.

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.00846% Admixed American · 5/59,094 alleles

Filtering AF 0.00327% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.00279%

Overall 0.00386% 62/1,604,158 alleles · very rare

Ancestry group	Frequency	1 in
Admixed Americangrpmax	0.00846%	11,819
Remaining individualsnot grpmax-eligible	0.00482%	20,735
South Asian	0.00445%	22,449
European (non-Finnish)	0.00408%	24,526
Finnishnot grpmax-eligible	0.00167%	59,912
African / African-American	0.00134%	74,846

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.Arg62His
Coding: c.185G>A
MANE Select: NM_004055
dbSNP: rs199504989
Type: single nucleotide variant
Location: chr11:77093701 (GRCh38)
Gene constraint: LOEUF 0.928 · pLI <0.01 · ClinGen HI 0/3 (gnomAD)
Structure: AlphaFold pLDDT 91.71 · 1 PDB
Residue 62: the calpain catalytic domain

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

Also linked: inherited retinal dystrophy

Similar variants

OMP p.Arg62Trp Uncertain significance ★ ⚠ same residue
CAPN5 p.Arg62= 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

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-arg62his (accessed [today's date]).

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