Is DMD p.Asp725Tyr (c.2173G>T) pathogenic?

DMD p.Asp725Tyr (c.2173G>T) is classified Benign/Likely benign in DMD (ClinVar, Multiple submitters, 7 submitters; last evaluated 2025-12-08). AlphaMissense: likely pathogenic (0.625); Rare (popmax 0.286%, sas); Associated with Cardiovascular phenotype.

What condition is associated with DMD p.Asp725Tyr (c.2173G>T)?

DMD p.Asp725Tyr (c.2173G>T) is associated with Cardiovascular phenotype, cardiomyopathy, Becker muscular dystrophy (ClinVar).

How common is DMD p.Asp725Tyr (c.2173G>T) in the general population?

DMD p.Asp725Tyr (c.2173G>T) is rare (popmax 0.286%, sas) (gnomAD).

What do computational predictors say about DMD p.Asp725Tyr (c.2173G>T)?

AlphaMissense predicts likely pathogenic (score 0.625) — an in-silico prediction, not a clinical call.

DMD p.Asp725Tyr

c.2173G>T · rs398123879 · VCV94498

Benign/Likely benign Multiple submitters

Classification

Benign/Likely benign

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 7 submitters

AlphaMissense

likely pathogenic

0.625 · ACMG-weighted

gnomAD v4.1

Rare

rare (popmax 0.286%, sas)

Conditions

Cardiovascular phenotype

Computational evidence

Protein change
AlphaMissense	0.625	likely pathogenic
REVEL	0.4	indeterminate
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 7.7	GERP 1.3, phastCons 1
Regional constraint	o/e 1.36	unconstrained · MANE · 1,863 kb · p 2.4e-62 · regional, not allelic
Overall
CADD	26.7	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 0.286% South Asian · 162/56,646 alleles

Filtering AF 0.25% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.236%

Overall 0.0144% 174/1,207,173 alleles · rare

Ancestry group	Frequency	1 in
South Asiangrpmax	0.286%	350
Middle Eastern	0.023%	4,344
Remaining individualsnot grpmax-eligible	0.0189%	5,281
African / African-American	0.00175%	57,168
European (non-Finnish)	0.000112%	892,905

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.Asp725Tyr
Coding: c.2173G>T
MANE Select: NM_004006
dbSNP: rs398123879
Type: single nucleotide variant
Location: chrX:32518127 (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.Asp725Asn Uncertain significance ★ ⚠ same residue
DMD p.Asp725His Uncertain significance ★ ⚠ same residue
DMD p.Asp725= 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
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-asp725tyr (accessed [today's date]).

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