Is CAPN15 p.Arg428Gln (c.1283G>A) pathogenic?

CAPN15 p.Arg428Gln (c.1283G>A) is classified Likely benign in CAPN15 (ClinVar, No assertion criteria, 2 submitters; last evaluated 2022-12-13). AlphaMissense: likely benign (0.0736); Rare (popmax 0.387%, afr); Associated with CAPN15-related disorder.

What condition is associated with CAPN15 p.Arg428Gln (c.1283G>A)?

CAPN15 p.Arg428Gln (c.1283G>A) is associated with CAPN15-related disorder (ClinVar).

How common is CAPN15 p.Arg428Gln (c.1283G>A) in the general population?

CAPN15 p.Arg428Gln (c.1283G>A) is rare (popmax 0.387%, afr) (gnomAD).

What do computational predictors say about CAPN15 p.Arg428Gln (c.1283G>A)?

AlphaMissense predicts likely benign (score 0.0736) — an in-silico prediction, not a clinical call.

CAPN15 p.Arg428Gln

c.1283G>A · rs202055221 · VCV3039007

Likely benign No assertion criteria

Classification

Likely benign

ClinVar

Review

No assertion criteria ☆☆☆☆

ClinVar · 2 submitters

AlphaMissense

likely benign

0.0736 · ACMG-weighted

gnomAD v4.1

Rare

rare (popmax 0.387%, afr)

Missense predictors

0/3 damaging

AlphaMissense, REVEL, SaProt

Conditions

CAPN15-related disorder

Computational evidence

Protein change
AlphaMissense	0.0736	likely benign
REVEL	0.116	moderately benign-leaning
SaProt	LLR -4.87	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 3.3	GERP -1.5, phastCons 0.86
Regional constraint	o/e 1.14	unconstrained · MANE · 2,296 bp · p 0.00013 · regional, not allelic
Overall
CADD	16.73	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 0.387% African / African-American · 279/72,082 alleles

Filtering AF 0.35% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.335%

Overall 0.0207% 318/1,535,662 alleles · rare

Ancestry group	Frequency	1 in
African / African-Americangrpmax	0.387%	258
Remaining individualsnot grpmax-eligible	0.0254%	3,937
Middle Eastern	0.0171%	5,844
Admixed American	0.0159%	6,306
East Asian	0.00487%	20,539
European (non-Finnish)	0.00114%	87,865

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: CAPN15
Protein: p.Arg428Gln
Coding: c.1283G>A
MANE Select: NM_005632
dbSNP: rs202055221
Type: single nucleotide variant
Location: chr16:548121 (GRCh38)
Gene constraint: LOEUF 0.974 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 71.65

Full CAPN15 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Disease context

CAPN15-related disorder

Similar variants

CAPN15 p.Arg428Trp Uncertain significance ★★ ⚠ same residue
CAPN15 p.Pro494Ser Uncertain significance ★ ⚠ same condition
CAPN15 p.Ser613Leu Conflicting classifications of pathogenicity ★ ⚠ same condition
CAPN15 p.Thr950Ala Uncertain significance ⚠ same condition
CAPN15 p.Ala559= Likely benign same condition
CAPN15 p.Ala817= Likely benign same condition
CAPN15 p.Asn745= Likely benign same condition
CAPN15 p.Asp590= Benign 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/capn15-p-arg428gln (accessed [today's date]).

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