Is DMD p.Arg149Cys (c.445C>T) pathogenic?

DMD p.Arg149Cys (c.445C>T) is classified Conflicting classifications of pathogenicity in DMD (ClinVar, Conflicting submitters, 3 submitters; last evaluated 2024-11-03). AlphaMissense: likely benign (0.1317); Very rare (popmax 0.00296%, eas); Associated with Cardiovascular phenotype.

What condition is associated with DMD p.Arg149Cys (c.445C>T)?

DMD p.Arg149Cys (c.445C>T) is associated with Cardiovascular phenotype, cardiomyopathy, Becker muscular dystrophy (ClinVar).

How common is DMD p.Arg149Cys (c.445C>T) in the general population?

DMD p.Arg149Cys (c.445C>T) is very rare (popmax 0.00296%, eas) (gnomAD).

What do computational predictors say about DMD p.Arg149Cys (c.445C>T)?

AlphaMissense predicts likely benign (score 0.1317) — an in-silico prediction, not a clinical call.

DMD p.Arg149Cys

c.445C>T · rs774139970 · VCV644000

Conflicting classifications of pathogenicity Conflicting submitters

Classification

Conflicting classifications of pathogenicity

ClinVar

Review

Conflicting submitters ★☆☆☆

ClinVar · 3 submitters

AlphaMissense

likely benign

0.1317 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 0.00296%, eas)

Missense predictors

1/2 damaging

AlphaMissense, REVEL

Conditions

Cardiovascular phenotype

Computational evidence

Protein change
AlphaMissense	0.1317	likely benign
REVEL	0.737	pathogenic-leaning
⇒ REVEL calls this damaging; AlphaMissense does not.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 12	GERP -0.21, phastCons 1
Regional constraint	o/e 1.36	unconstrained · MANE · 1,863 kb · p 2.4e-62 · regional, not allelic
Overall
CADD	33.0	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 0.00296% East Asian · 1/33,840 alleles

Filtering AF 8.9e-05% ClinGen BA1/BS1 input FAF95, joint · FAF99 2.5e-05%

Overall 0.000364% 4/1,097,578 alleles · very rare

Ancestry group	Frequency	1 in
East Asiangrpmax	0.00296%	33,840
European (non-Finnish)	0.000335%	298,312

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.Arg149Cys
Coding: c.445C>T
MANE Select: NM_004006
dbSNP: rs774139970
Type: single nucleotide variant
Location: chrX:32816553 (GRCh38)
Residue 149: a turn; the calponin-homology (ch) 2 domain; the 'actin-binding' region

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.Arg149His Uncertain significance ★★ same residue
DMD p.Arg149Leu Uncertain significance ★ same residue
DMD p.Arg149Pro Uncertain significance ★ ⚠ same residue
DMD p.Arg149Ser Conflicting classifications of pathogenicity ★ same residue
DMD p.Arg149= Likely benign ★ same residue
DMD p.Arg149fs Pathogenic ★ same residue
DMD c.10086+1G>A Pathogenic ★★ same condition
DMD c.10086+1G>T 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-arg149cys (accessed [today's date]).

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