Is DMD p.Arg943His (c.2828G>A) pathogenic?

DMD p.Arg943His (c.2828G>A) is classified Conflicting classifications of pathogenicity in DMD (ClinVar, Conflicting submitters, 5 submitters; last evaluated 2026-01-19). AlphaMissense: likely benign (0.0762); Ultra-rare (popmax 0.0406%, sas); Associated with Duchenne muscular dystrophy.

What condition is associated with DMD p.Arg943His (c.2828G>A)?

DMD p.Arg943His (c.2828G>A) is associated with Duchenne muscular dystrophy, cardiomyopathy, Becker muscular dystrophy (ClinVar).

How common is DMD p.Arg943His (c.2828G>A) in the general population?

DMD p.Arg943His (c.2828G>A) is ultra-rare (popmax 0.0406%, 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.Arg943His (c.2828G>A)?

AlphaMissense predicts likely benign (score 0.0762) — an in-silico prediction, not a clinical call.

DMD p.Arg943His

c.2828G>A · rs398123911 · VCV94540

Conflicting classifications of pathogenicity Conflicting submitters

Classification

Conflicting classifications of pathogenicity

ClinVar

Review

Conflicting submitters ★☆☆☆

ClinVar · 5 submitters

AlphaMissense

likely benign

0.0762 · ACMG-weighted

gnomAD v4.1

Rare

ultra-rare (popmax 0.0406%, sas)

Missense predictors

0/2 damaging

AlphaMissense, REVEL

Conditions

Duchenne muscular dystrophy

Computational evidence

Protein change
AlphaMissense	0.0762	likely benign
REVEL	0.027	moderately benign-leaning
⇒ AlphaMissense and REVEL both call this tolerated.
Splicing
SpliceAI	<0.2	all four deltas below 0.2 · C>A here scores Δ0.47 · evaluated, not missing
Constraint at this position
Conservation	phyloP 1.7	GERP 1.2, phastCons 1
Regional constraint	o/e 1.36	unconstrained · MANE · 1,863 kb · p 2.4e-62 · regional, not allelic
Overall
CADD	16.88	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 0.0406% South Asian · 23/56,718 alleles

Filtering AF 0.0277% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.0235%

Overall 0.00372% 45/1,208,496 alleles · ultra-rare

Ancestry group	Frequency	1 in
South Asiangrpmax	0.0406%	2,466
Remaining individualsnot grpmax-eligible	0.00841%	11,885
East Asian	0.00297%	33,712
Admixed American	0.00219%	45,561
African / African-American	0.00176%	56,825
European (non-Finnish)	0.00168%	59,644

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.Arg943His
Coding: c.2828G>A
MANE Select: NM_004006
dbSNP: rs398123911
Type: single nucleotide variant
Location: chrX:32472285 (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.Arg943Cys Conflicting classifications of pathogenicity ★ same residue
DMD p.Arg943= Likely benign ★ same residue
DMD p.Arg943Pro Uncertain significance ★ ⚠ same residue
DMD p.Arg943Ser 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

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-arg943his (accessed [today's date]).

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