Is DMD p.Cys569Ser (c.1705T>A) pathogenic?

DMD p.Cys569Ser (c.1705T>A) is classified Uncertain significance in DMD (ClinVar, No assertion criteria, 1 submitter; last evaluated 2025-04-08). AlphaMissense: likely benign (0.1186); Absent from gnomAD v4.1; Associated with Becker muscular dystrophy, Cardiomyopathy, Duchenne muscular dystrophy, Dystrophin deficiency.

How common is DMD p.Cys569Ser (c.1705T>A) in the general population?

DMD p.Cys569Ser (c.1705T>A) is absent from gnomAD v4.1 (gnomAD).

What do computational predictors say about DMD p.Cys569Ser (c.1705T>A)?

AlphaMissense predicts likely benign (score 0.1186) — an in-silico prediction, not a clinical call.

DMD p.Cys569Ser

Q: What condition is associated with DMD p.Cys569Ser (c.1705T>A)?

DMD p.Cys569Ser (c.1705T>A) is associated with Becker muscular dystrophy, Cardiomyopathy, Duchenne muscular dystrophy, Dystrophin deficiency (ClinVar).

c.1705T>A · VCV4066195

Uncertain significance No assertion criteria

Classification

Uncertain significance

ClinVar

Review

No assertion criteria ☆☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.1186 · ACMG-weighted

gnomAD v4.1

Absent

absent from gnomAD v4.1

Missense predictors

0/2 damaging

AlphaMissense, REVEL · SaProt no call

Conditions

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

Computational evidence

Protein change
AlphaMissense	0.1186	likely benign
REVEL	0.141	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 11	GERP 1.9, phastCons 1
Regional constraint	o/e 1.36	unconstrained · MANE · 1,863 kb · p 2.4e-62 · regional, not allelic
Overall
CADD	19.76	PHRED · no single calibrated threshold — expert panels disagree

ClinVar classifies this uncertain; the computational predictors unanimously lean tolerated — a triage signal, not a reclassification

AlphaMissense carries the ACMG weight for missense; REVEL is an independent agreement signal.

Population frequency

gnomAD v4.1 · exomes + genomes

Absent from gnomAD v4.1. Not observed in any sequenced alleles — a rarity signal (ACMG PM2-supporting), not evidence of pathogenicity on its own.

Variant & gene context

Gene: DMD
Protein: p.Cys569Ser
Coding: c.1705T>A
MANE Select: NM_004006
Type: single nucleotide variant
Location: chrX:32573637 (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

Similar variants

DMD p.Cys569= Likely benign ★★ same residue
DMD c.10223+1G>A Pathogenic ★★ same condition
DMD c.10224-2A>G Likely pathogenic ★★ same condition
DMD c.10797+1G>A Pathogenic ★★ same condition
DMD c.1150-1G>A Pathogenic ★★ same condition
DMD c.1483-1G>A Likely pathogenic ★★ same condition
DMD c.1603-2A>C Pathogenic/Likely pathogenic ★★ same condition
DMD c.1705-2A>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-cys569ser (accessed [today's date]).

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