Is DMD p.Leu575Pro (c.1724T>C) pathogenic?

DMD p.Leu575Pro (c.1724T>C) is classified Conflicting classifications of pathogenicity in DMD (ClinVar, Conflicting submitters, 17 submitters; last evaluated 2026-01-06). AlphaMissense: likely pathogenic (0.9279); Very rare (popmax 0.00219%, amr); Associated with Becker muscular dystrophy, Cardiomyopathy, Duchenne muscular dystrophy, Dystrophin deficiency.

How common is DMD p.Leu575Pro (c.1724T>C) in the general population?

DMD p.Leu575Pro (c.1724T>C) is very rare (popmax 0.00219%, amr) (gnomAD).

What do computational predictors say about DMD p.Leu575Pro (c.1724T>C)?

AlphaMissense predicts likely pathogenic (score 0.9279) — an in-silico prediction, not a clinical call.

DMD p.Leu575Pro

Q: What condition is associated with DMD p.Leu575Pro (c.1724T>C)?

DMD p.Leu575Pro (c.1724T>C) is associated with Becker muscular dystrophy, Cardiomyopathy, Duchenne muscular dystrophy, Dystrophin deficiency, Becker muscular dystrophy, dilated cardiomyopathy 3B (ClinVar).

c.1724T>C · rs370644567 · VCV161220

Conflicting classifications of pathogenicity Conflicting submitters

Classification

Conflicting classifications of pathogenicity

ClinVar

Review

Conflicting submitters ★☆☆☆

ClinVar · 17 submitters

AlphaMissense

likely pathogenic

0.9279 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 0.00219%, amr)

Missense predictors

2/2 damaging

AlphaMissense, REVEL

Conditions

Becker muscular dystrophy, Cardiomyopathy, Duchenne muscular dystrophy, Dystrophin deficiency

Computational evidence

Protein change
AlphaMissense	0.9279	likely pathogenic · top 10% in DMD
REVEL	0.775	moderately pathogenic-leaning
⇒ AlphaMissense and REVEL both call this damaging.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 11	GERP 1.8, phastCons 1
Regional constraint	o/e 1.36	unconstrained · MANE · 1,863 kb · p 2.4e-62 · regional, not allelic
Overall
CADD	27.2	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 0.00219% Admixed American · 1/45,715 alleles

Filtering AF 0.00136% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.0011%

Overall 0.00174% 21/1,209,011 alleles · very rare

Ancestry group	Frequency	1 in
Admixed Americangrpmax	0.00219%	45,715
European (non-Finnish)	0.00213%	47,057
African / African-American	0.00175%	57,282

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.Leu575Pro
Coding: c.1724T>C
MANE Select: NM_004006
dbSNP: rs370644567
Type: single nucleotide variant
Location: chrX:32573618 (GRCh38)

Full DMD gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Disease context

Becker muscular dystrophy, Cardiomyopathy, Duchenne muscular dystrophy, Dystrophin deficiency

Also linked: Becker muscular dystrophy dilated cardiomyopathy 3B Duchenne muscular dystrophy neuromuscular disease caused by qualitative or quantitative defects of dystrophin muscular dystrophy

Similar variants

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
DMD c.10223+1G>C Pathogenic ★★ same condition
DMD c.10224-2A>G Likely pathogenic ★★ same condition
DMD c.10554-2A>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-leu575pro (accessed [today's date]).

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