Is DMD p.Arg3489His (c.10466G>A) pathogenic?

DMD p.Arg3489His (c.10466G>A) is classified Uncertain significance in DMD (ClinVar, Single submitter, 1 submitter; last evaluated 2023-10-04). AlphaMissense: likely benign (0.1646); Very rare (popmax 0.00178%, sas); Associated with Duchenne muscular dystrophy.

What condition is associated with DMD p.Arg3489His (c.10466G>A)?

DMD p.Arg3489His (c.10466G>A) is associated with Duchenne muscular dystrophy (ClinVar).

How common is DMD p.Arg3489His (c.10466G>A) in the general population?

DMD p.Arg3489His (c.10466G>A) is very rare (popmax 0.00178%, sas) (gnomAD).

How is Duchenne muscular dystrophy inherited?

Typically X-linked recessive (Orphanet). A genetic counselor can assess individual risk for a family.

What do computational predictors say about DMD p.Arg3489His (c.10466G>A)?

AlphaMissense predicts likely benign (score 0.1646) — an in-silico prediction, not a clinical call.

DMD p.Arg3489His

c.10466G>A · rs1297635532 · VCV1375535

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.1646 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 0.00178%, sas)

Conditions

Duchenne muscular dystrophy

Computational evidence

Protein change
AlphaMissense	0.1646	likely benign
REVEL	0.344	indeterminate
SaProt	—	not scored · why
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 4.9	GERP 1.3, phastCons 1
Regional constraint	o/e 0.57	unconstrained · MANE · 25 kb · p 7.9e-06 · regional, not allelic
Overall
CADD	27.4	PHRED · no single calibrated threshold — expert panels disagree

AlphaMissense carries the ACMG weight for missense; REVEL is an independent agreement signal.

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.00178% South Asian · 1/56,286 alleles

Filtering AF 0.000105% ClinGen BA1/BS1 input FAF95, joint · FAF99 7.1e-05%

Overall 0.000458% 5/1,091,138 alleles · very rare

Ancestry group	Frequency	1 in
South Asiangrpmax	0.00178%	56,286
European (non-Finnish)	0.000449%	222,514

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.Arg3489His
Coding: c.10466G>A
MANE Select: NM_004006
dbSNP: rs1297635532
Type: single nucleotide variant
Location: chrX:31169530 (GRCh38)
Residue 3489: the 'binds to sntb1' region

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

Disease context

Duchenne muscular dystrophy — disease report on Sugi Atlas → Associated genes, phenotypes, clinical trials & treatments

For Duchenne muscular dystrophy (Orphanet):

Inheritance: X-linked recessive
Onset: Childhood
Prevalence: 1-9 / 100 000 (Worldwide)

Similar variants

DMD p.Arg3489Cys Conflicting classifications of pathogenicity ★ 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
DMD c.10223+1G>A Pathogenic ★★ same condition
DMD c.10223+1G>C Pathogenic ★★ same condition
DMD c.10224-2A>G 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-arg3489his (accessed [today's date]).

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