Is DMD p.Arg488Cys (c.1462C>T) pathogenic?

DMD p.Arg488Cys (c.1462C>T) is classified Benign/Likely benign in DMD (ClinVar, Multiple submitters, 9 submitters; last evaluated 2026-01-13). AlphaMissense: likely benign (0.0775); Very rare (popmax 0.00896%, nfe); Associated with Cardiovascular phenotype.

What condition is associated with DMD p.Arg488Cys (c.1462C>T)?

DMD p.Arg488Cys (c.1462C>T) is associated with Cardiovascular phenotype, long QT syndrome, cardiomyopathy (ClinVar).

How common is DMD p.Arg488Cys (c.1462C>T) in the general population?

DMD p.Arg488Cys (c.1462C>T) is very rare (popmax 0.00896%, nfe) (gnomAD).

What do computational predictors say about DMD p.Arg488Cys (c.1462C>T)?

AlphaMissense predicts likely benign (score 0.0775) — an in-silico prediction, not a clinical call.

DMD p.Arg488Cys

c.1462C>T · rs758932385 · VCV391751

Benign/Likely benign Multiple submitters

Classification

Benign/Likely benign

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 9 submitters

AlphaMissense

likely benign

0.0775 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 0.00896%, nfe)

Missense predictors

0/2 damaging

AlphaMissense, REVEL

Conditions

Cardiovascular phenotype

Computational evidence

Protein change
AlphaMissense	0.0775	likely benign
REVEL	0.057	moderately benign-leaning
⇒ AlphaMissense and REVEL both call this tolerated.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 2.1	GERP -1, phastCons 1
Regional constraint	o/e 1.36	unconstrained · MANE · 1,863 kb · p 2.4e-62 · regional, not allelic
Overall
CADD	18.54	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 0.00896% European (non-Finnish) · 80/893,263 alleles

Filtering AF 0.00732% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.00678%

Overall 0.00763% 92/1,205,796 alleles · very rare

Ancestry group	Frequency	1 in
European (non-Finnish)grpmax	0.00896%	11,166
Admixed American	0.00883%	11,330
Remaining individualsnot grpmax-eligible	0.00632%	15,811
South Asian	0.0053%	18,883
African / African-American	0.00354%	28,234

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: DMD
Protein: p.Arg488Cys
Coding: c.1462C>T
MANE Select: NM_004006
dbSNP: rs758932385
Type: single nucleotide variant
Location: chrX:32614323 (GRCh38)

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

Disease context

Cardiovascular phenotype — disease report on Sugi Atlas → Associated genes, phenotypes, clinical trials & treatments

Also linked: long QT syndrome cardiomyopathy Becker muscular dystrophy dilated cardiomyopathy 3B Duchenne muscular dystrophy Brugada syndrome

Similar variants

DMD p.Arg488His Conflicting classifications of pathogenicity ★ ⚠ same residue
DMD p.Arg488Leu Conflicting classifications of pathogenicity ★ ⚠ same residue
DMD p.Arg488= Likely benign ★ same residue
DMD p.Arg488Ser Uncertain significance ★★ ⚠ same residue
DMD c.10086+1G>A Pathogenic ★★ same condition
DMD c.10086+1G>T Pathogenic ★★ same condition
DMD c.10086+2T>C Pathogenic ★★ same condition
DMD c.10087-2A>G Pathogenic/Likely pathogenic ★★ 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/dmd-p-arg488cys (accessed [today's date]).

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