Is DMD p.Gln85Arg (c.254A>G) pathogenic?

DMD p.Gln85Arg (c.254A>G) is classified Uncertain significance in DMD (ClinVar, Multiple submitters, 3 submitters; last evaluated 2025-12-21). AlphaMissense: likely benign (0.1468); Ultra-rare (popmax 0.0193%, sas); Associated with Duchenne muscular dystrophy.

What condition is associated with DMD p.Gln85Arg (c.254A>G)?

DMD p.Gln85Arg (c.254A>G) is associated with Duchenne muscular dystrophy, cardiomyopathy, Becker muscular dystrophy (ClinVar).

How common is DMD p.Gln85Arg (c.254A>G) in the general population?

DMD p.Gln85Arg (c.254A>G) is ultra-rare (popmax 0.0193%, 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.Gln85Arg (c.254A>G)?

AlphaMissense predicts likely benign (score 0.1468) — an in-silico prediction, not a clinical call.

DMD p.Gln85Arg

c.254A>G · rs1297662991 · VCV572269

Uncertain significance Multiple submitters

Classification

Uncertain significance

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 3 submitters

AlphaMissense

likely benign

0.1468 · ACMG-weighted

gnomAD v4.1

Rare

ultra-rare (popmax 0.0193%, sas)

Conditions

Duchenne muscular dystrophy

Computational evidence

Protein change
AlphaMissense	0.1468	likely benign
REVEL	0.595	indeterminate
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 5.1	GERP 2.1, phastCons 1
Regional constraint	o/e 1.36	unconstrained · MANE · 1,863 kb · p 2.4e-62 · regional, not allelic
Overall
CADD	22.6	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 0.0193% South Asian · 11/56,967 alleles

Filtering AF 0.0108% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.00833%

Overall 0.00128% 14/1,096,600 alleles · ultra-rare

Ancestry group	Frequency	1 in
South Asiangrpmax	0.0193%	5,179
European (non-Finnish)	0.000336%	298,056

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.Gln85Arg
Coding: c.254A>G
MANE Select: NM_004006
dbSNP: rs1297662991
Type: single nucleotide variant
Location: chrX:32844793 (GRCh38)
Residue 85: the calponin-homology (ch) 1 domain; an α-helix; the 'actin-binding' 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

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.Gln85= Likely benign ★ same residue
DMD p.Gln85Ter Pathogenic 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-gln85arg (accessed [today's date]).

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