Is DMD p.Arg649Trp (c.1945C>T) pathogenic?

DMD p.Arg649Trp (c.1945C>T) is classified Likely benign in DMD (ClinVar, Multiple submitters, 5 submitters; last evaluated 2026-01-28). AlphaMissense: likely benign (0.101); Ultra-rare (popmax 0.0118%, eas); Associated with Cardiovascular phenotype.

What condition is associated with DMD p.Arg649Trp (c.1945C>T)?

DMD p.Arg649Trp (c.1945C>T) is associated with Cardiovascular phenotype, cardiomyopathy, Becker muscular dystrophy (ClinVar).

How common is DMD p.Arg649Trp (c.1945C>T) in the general population?

DMD p.Arg649Trp (c.1945C>T) is ultra-rare (popmax 0.0118%, eas) (gnomAD).

What do computational predictors say about DMD p.Arg649Trp (c.1945C>T)?

AlphaMissense predicts likely benign (score 0.101) — an in-silico prediction, not a clinical call.

DMD p.Arg649Trp

c.1945C>T · rs770572107 · VCV697997

Likely benign Multiple submitters

Classification

Likely benign

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 5 submitters

AlphaMissense

likely benign

0.101 · ACMG-weighted

gnomAD v4.1

Rare

ultra-rare (popmax 0.0118%, eas)

Missense predictors

0/2 damaging

AlphaMissense, REVEL · SaProt no call

Conditions

Cardiovascular phenotype

Computational evidence

Protein change
AlphaMissense	0.101	likely benign
REVEL	0.123	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 5	GERP -0.099, phastCons 1
Regional constraint	o/e 1.36	unconstrained · MANE · 1,863 kb · p 2.4e-62 · regional, not allelic
Overall
CADD	22.9	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 0.0118% East Asian · 4/33,760 alleles

Filtering AF 0.00396% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.00236%

Overall 0.00231% 28/1,209,612 alleles · ultra-rare exomes 25/1,097,980 · genomes 3/111,632 · joint denominator

Ancestry group	Frequency	1 in
East Asiangrpmax	0.0118%	8,440
Remaining individualsnot grpmax-eligible	0.0042%	23,791
South Asian	0.00352%	28,420
European (non-Finnish)	0.00223%	44,751

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.Arg649Trp
Coding: c.1945C>T
MANE Select: NM_004006
dbSNP: rs770572107
Type: single nucleotide variant
Location: chrX:32565749 (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.Arg649= Likely benign ★★ same residue
DMD p.Arg649Leu Uncertain significance ★ ⚠ same residue
DMD p.Arg649Pro Uncertain significance ★ same residue
DMD p.Arg649Gln Likely benign ★ 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-arg649trp (accessed [today's date]).

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