Is CAPN5 p.Arg411Gln (c.1232G>A) pathogenic?

CAPN5 p.Arg411Gln (c.1232G>A) is classified Conflicting classifications of pathogenicity in CAPN5 (ClinVar, Conflicting submitters, 3 submitters; last evaluated 2024-09-04). AlphaMissense: likely benign (0.067); Ultra-rare (popmax 0.0317%, amr); Associated with Inborn genetic diseases.

What condition is associated with CAPN5 p.Arg411Gln (c.1232G>A)?

CAPN5 p.Arg411Gln (c.1232G>A) is associated with Inborn genetic diseases (ClinVar).

How common is CAPN5 p.Arg411Gln (c.1232G>A) in the general population?

CAPN5 p.Arg411Gln (c.1232G>A) is ultra-rare (popmax 0.0317%, amr) (gnomAD).

What do computational predictors say about CAPN5 p.Arg411Gln (c.1232G>A)?

AlphaMissense predicts likely benign (score 0.067) — an in-silico prediction, not a clinical call.

CAPN5 p.Arg411Gln

c.1232G>A · rs782372843 · VCV1035337

Conflicting classifications of pathogenicity Conflicting submitters

Classification

Conflicting classifications of pathogenicity

ClinVar

Review

Conflicting submitters ★☆☆☆

ClinVar · 3 submitters

AlphaMissense

likely benign

0.067 · ACMG-weighted

gnomAD v4.1

Rare

ultra-rare (popmax 0.0317%, amr)

Missense predictors

0/2 damaging

AlphaMissense, SaProt · REVEL no call

Conditions

Inborn genetic diseases

Computational evidence

Protein change
AlphaMissense	0.067	likely benign
REVEL	0.48	indeterminate
SaProt	LLR -9.37	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 8.5	GERP 0.45, phastCons 1
Regional constraint	o/e 0.89	unconstrained · MANE · 39 kb · p 0.00098 · regional, not allelic
Overall
CADD	23.3	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 0.0317% Admixed American · 19/60,002 alleles

Filtering AF 0.0207% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.0172%

Overall 0.00297% 48/1,613,940 alleles · ultra-rare

Ancestry group	Frequency	1 in
Admixed Americangrpmax	0.0317%	3,158
South Asian	0.0121%	8,275
East Asian	0.00668%	14,965
European (non-Finnish)	0.00127%	78,666

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.Arg411Gln
Coding: c.1232G>A
MANE Select: NM_004055
dbSNP: rs782372843
Type: single nucleotide variant
Location: chr11:77119094 (GRCh38)
Gene constraint: LOEUF 0.928 · pLI <0.01 · ClinGen HI 0/3 (gnomAD)
Structure: AlphaFold pLDDT 91.71 · 1 PDB
Residue 411: the 'domain iii' region

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.Arg411Trp Uncertain significance ★ ⚠ same residue
CAPN5 p.Arg411= 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-arg411gln (accessed [today's date]).

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