Is DMD p.Arg1016Gln (c.3047G>A) pathogenic?

DMD p.Arg1016Gln (c.3047G>A) is classified Conflicting classifications of pathogenicity in DMD (ClinVar, Conflicting submitters, 4 submitters; last evaluated 2025-09-05). AlphaMissense: likely benign (0.0585); Ultra-rare (popmax 0.0458%, sas); Associated with Cardiovascular phenotype.

What condition is associated with DMD p.Arg1016Gln (c.3047G>A)?

DMD p.Arg1016Gln (c.3047G>A) is associated with Cardiovascular phenotype, cardiomyopathy, Becker muscular dystrophy (ClinVar).

How common is DMD p.Arg1016Gln (c.3047G>A) in the general population?

DMD p.Arg1016Gln (c.3047G>A) is ultra-rare (popmax 0.0458%, sas) (gnomAD).

What do computational predictors say about DMD p.Arg1016Gln (c.3047G>A)?

AlphaMissense predicts likely benign (score 0.0585) — an in-silico prediction, not a clinical call.

DMD p.Arg1016Gln

c.3047G>A · rs139772014 · VCV282310

Conflicting classifications of pathogenicity Conflicting submitters

Classification

Conflicting classifications of pathogenicity

ClinVar

Review

Conflicting submitters ★☆☆☆

ClinVar · 4 submitters

AlphaMissense

likely benign

0.0585 · ACMG-weighted

gnomAD v4.1

Rare

ultra-rare (popmax 0.0458%, sas)

Missense predictors

0/2 damaging

AlphaMissense, REVEL

Conditions

Cardiovascular phenotype

Computational evidence

Protein change
AlphaMissense	0.0585	likely benign
REVEL	0.052	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 -3.4	GERP -4.3
Regional constraint	o/e 1.36	unconstrained · MANE · 1,863 kb · p 2.4e-62 · regional, not allelic
Overall
CADD	0.034	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 0.0458% South Asian · 26/56,772 alleles

Filtering AF 0.032% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.0274%

Overall 0.00612% 74/1,208,870 alleles · ultra-rare

Ancestry group	Frequency	1 in
South Asiangrpmax	0.0458%	2,184
African / African-American	0.00701%	14,261
Remaining individualsnot grpmax-eligible	0.00631%	15,845
European (non-Finnish)	0.00447%	22,367
Admixed American	0.0022%	45,557

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.Arg1016Gln
Coding: c.3047G>A
MANE Select: NM_004006
dbSNP: rs139772014
Type: single nucleotide variant
Location: chrX:32468613 (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: cardiomyopathy Becker muscular dystrophy Duchenne muscular dystrophy

Similar variants

DMD p.Arg1016Trp Conflicting classifications of pathogenicity ★ ⚠ same residue
DMD p.Arg1016= Likely benign ★ same residue
DMD p.Arg1016fs 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

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-arg1016gln (accessed [today's date]).

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