Is DMD p.Arg3000His (c.8999G>A) pathogenic?

DMD p.Arg3000His (c.8999G>A) is classified Conflicting classifications of pathogenicity in DMD (ClinVar, Conflicting submitters, 3 submitters; last evaluated 2024-10-16). AlphaMissense: likely benign (0.0601); Ultra-rare (popmax 0.0211%, sas); Associated with Duchenne muscular dystrophy.

What condition is associated with DMD p.Arg3000His (c.8999G>A)?

DMD p.Arg3000His (c.8999G>A) is associated with Duchenne muscular dystrophy, cardiomyopathy, Becker muscular dystrophy (ClinVar).

How common is DMD p.Arg3000His (c.8999G>A) in the general population?

DMD p.Arg3000His (c.8999G>A) is ultra-rare (popmax 0.0211%, 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.Arg3000His (c.8999G>A)?

AlphaMissense predicts likely benign (score 0.0601) — an in-silico prediction, not a clinical call.

DMD p.Arg3000His

c.8999G>A · rs772695216 · VCV285683

Conflicting classifications of pathogenicity Conflicting submitters

Classification

Conflicting classifications of pathogenicity

ClinVar

Review

Conflicting submitters ★☆☆☆

ClinVar · 3 submitters

AlphaMissense

likely benign

0.0601 · ACMG-weighted

gnomAD v4.1

Rare

ultra-rare (popmax 0.0211%, sas)

Missense predictors

0/2 damaging

AlphaMissense, REVEL · SaProt no call

Conditions

Duchenne muscular dystrophy

Computational evidence

Protein change
AlphaMissense	0.0601	likely benign
REVEL	0.067	moderately benign-leaning
SaProt	—	not scored · why
⇒ AlphaMissense and REVEL both call this tolerated; SaProt makes no call.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 2.8	GERP 0.85, phastCons 1
Regional constraint	o/e 1.36	unconstrained · MANE · 1,863 kb · p 2.4e-62 · regional, not allelic
Overall
CADD	18.51	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 0.0211% South Asian · 12/56,957 alleles

Filtering AF 0.0121% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.00953%

Overall 0.00146% 16/1,097,932 alleles · ultra-rare

Ancestry group	Frequency	1 in
South Asiangrpmax	0.0211%	4,746
African / African-American	0.00346%	28,884
East Asian	0.00296%	33,824
European (non-Finnish)	0.000112%	895,303

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.Arg3000His
Coding: c.8999G>A
MANE Select: NM_004006
dbSNP: rs772695216
Type: single nucleotide variant
Location: chrX:31444566 (GRCh38)

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

Also linked: cardiomyopathy Becker muscular dystrophy

For Duchenne muscular dystrophy (Orphanet):

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

Similar variants

DMD p.Arg3000Cys Conflicting classifications of pathogenicity ★ ⚠ same residue
DMD p.Arg3000Leu 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
DMD c.10223+1G>A Pathogenic ★★ same condition
DMD c.10223+1G>C 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-arg3000his (accessed [today's date]).

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