Is DMD p.Arg145Gln (c.434G>A) pathogenic?

DMD p.Arg145Gln (c.434G>A) is classified Conflicting classifications of pathogenicity in DMD (ClinVar, Conflicting submitters, 7 submitters; last evaluated 2026-01-12). AlphaMissense: ambiguous (0.409); Very rare (popmax 0.00749%, nfe); Associated with Cardiovascular phenotype.

What condition is associated with DMD p.Arg145Gln (c.434G>A)?

DMD p.Arg145Gln (c.434G>A) is associated with Cardiovascular phenotype, Duchenne muscular dystrophy (ClinVar).

How common is DMD p.Arg145Gln (c.434G>A) in the general population?

DMD p.Arg145Gln (c.434G>A) is very rare (popmax 0.00749%, nfe) (gnomAD).

What do computational predictors say about DMD p.Arg145Gln (c.434G>A)?

AlphaMissense predicts ambiguous (score 0.409) — an in-silico prediction, not a clinical call.

DMD p.Arg145Gln

c.434G>A · rs398123952 · VCV285293

Conflicting classifications of pathogenicity Conflicting submitters

Classification

Conflicting classifications of pathogenicity

ClinVar

Review

Conflicting submitters ★☆☆☆

ClinVar · 7 submitters

AlphaMissense

ambiguous

0.409 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 0.00749%, nfe)

Conditions

Cardiovascular phenotype

Computational evidence

Protein change
AlphaMissense	0.409	ambiguous
REVEL	0.706	pathogenic-leaning
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 7.6	GERP 2.4, phastCons 1
Regional constraint	o/e 1.36	unconstrained · MANE · 1,863 kb · p 2.4e-62 · regional, not allelic
Overall
CADD	28.7	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 0.00749% European (non-Finnish) · 67/894,873 alleles

Filtering AF 0.00598% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.00549%

Overall 0.00604% 73/1,209,540 alleles · very rare

Ancestry group	Frequency	1 in
European (non-Finnish)grpmax	0.00749%	13,356
Admixed American	0.00657%	15,232
African / African-American	0.0035%	28,577
Remaining individualsnot grpmax-eligible	0.0021%	47,575

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.Arg145Gln
Coding: c.434G>A
MANE Select: NM_004006
dbSNP: rs398123952
Type: single nucleotide variant
Location: chrX:32816564 (GRCh38)
Residue 145: an α-helix; 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: Duchenne muscular dystrophy

Similar variants

DMD p.Arg145Pro Pathogenic/Likely pathogenic ★★ same residue
DMD p.Arg145Ter Pathogenic ★★ same residue
DMD p.Arg145Gly Uncertain significance ★ ⚠ same residue
DMD p.Arg145= 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-arg145gln (accessed [today's date]).

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