Is DMD p.Arg751Gln (c.2252G>A) pathogenic?

DMD p.Arg751Gln (c.2252G>A) is classified Conflicting classifications of pathogenicity in DMD (ClinVar, Conflicting submitters, 4 submitters; last evaluated 2025-12-22). AlphaMissense: likely benign (0.1329); Very rare (popmax 0.00392%, nfe); Associated with Cardiovascular phenotype.

What condition is associated with DMD p.Arg751Gln (c.2252G>A)?

DMD p.Arg751Gln (c.2252G>A) is associated with Cardiovascular phenotype, Duchenne muscular dystrophy (ClinVar).

How common is DMD p.Arg751Gln (c.2252G>A) in the general population?

DMD p.Arg751Gln (c.2252G>A) is very rare (popmax 0.00392%, nfe) (gnomAD).

What do computational predictors say about DMD p.Arg751Gln (c.2252G>A)?

AlphaMissense predicts likely benign (score 0.1329) — an in-silico prediction, not a clinical call.

DMD p.Arg751Gln

c.2252G>A · rs747802164 · VCV389966

Conflicting classifications of pathogenicity Conflicting submitters

Classification

Conflicting classifications of pathogenicity

ClinVar

Review

Conflicting submitters ★☆☆☆

ClinVar · 4 submitters

AlphaMissense

likely benign

0.1329 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 0.00392%, nfe)

Missense predictors

0/2 damaging

AlphaMissense, REVEL

Conditions

Cardiovascular phenotype

Computational evidence

Protein change
AlphaMissense	0.1329	likely benign
REVEL	0.17	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 4.9	GERP 6.3, phastCons 1
Regional constraint	o/e 1.36	unconstrained · MANE · 1,863 kb · p 2.4e-62 · regional, not allelic
Overall
CADD	24.7	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 0.00392% European (non-Finnish) · 35/893,952 alleles

Filtering AF 0.00284% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.00252%

Overall 0.00323% 39/1,208,249 alleles · very rare

Ancestry group	Frequency	1 in
European (non-Finnish)grpmax	0.00392%	25,541
African / African-American	0.00351%	28,526
Admixed American	0.00219%	45,670
South Asian	0.00176%	56,754

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.Arg751Gln
Coding: c.2252G>A
MANE Select: NM_004006
dbSNP: rs747802164
Type: single nucleotide variant
Location: chrX:32518048 (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: Duchenne muscular dystrophy

Similar variants

DMD p.Arg751= Likely benign ★★ same residue
DMD p.Arg751Leu Uncertain significance ★ ⚠ same residue
DMD p.Arg751Trp 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

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-arg751gln (accessed [today's date]).

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