Is DMD p.Cys3337Ser (c.10009T>A) pathogenic?

DMD p.Cys3337Ser (c.10009T>A) is classified Uncertain significance in DMD (ClinVar, Single submitter, 1 submitter; last evaluated 2023-12-13). AlphaMissense: likely pathogenic (0.9998); Absent from gnomAD v4.1.

How common is DMD p.Cys3337Ser (c.10009T>A) in the general population?

DMD p.Cys3337Ser (c.10009T>A) is absent from gnomAD v4.1 (gnomAD).

What do computational predictors say about DMD p.Cys3337Ser (c.10009T>A)?

AlphaMissense predicts likely pathogenic (score 0.9998) — an in-silico prediction, not a clinical call.

DMD p.Cys3337Ser

c.10009T>A · VCV3365656

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely pathogenic

0.9998 · ACMG-weighted

gnomAD v4.1

Absent

absent from gnomAD v4.1

Missense predictors

2/2 damaging

AlphaMissense, REVEL · SaProt no call

Computational evidence

Protein change
AlphaMissense	0.9998	likely pathogenic · top 1% in DMD
REVEL	0.947	strongly pathogenic-leaning
SaProt	—	not scored · why
⇒ AlphaMissense and REVEL both call this damaging; SaProt makes no call.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 11	GERP 3.4, phastCons 1
Regional constraint	o/e 0.66	unconstrained · MANE · 170 kb · p 2.6e-08 · regional, not allelic
Overall
CADD	28.5	PHRED · no single calibrated threshold — expert panels disagree

ClinVar classifies this uncertain; the computational predictors unanimously lean damaging — 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.Cys3337Ser
Coding: c.10009T>A
MANE Select: NM_004006
Type: single nucleotide variant
Location: chrX:31180447 (GRCh38)
Residue 3337: the 'interaction with synm' region; a binding site

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

Similar variants

DMD p.Cys3337Phe Conflicting classifications of pathogenicity ★ ⚠ same residue
DMD p.Cys3337Tyr Conflicting classifications of pathogenicity ★ ⚠ same residue
DMD c.10086+1G>A Pathogenic ★★ same type
DMD c.10086+1G>T Pathogenic ★★ same type
DMD c.10086+2T>C Pathogenic ★★ same type
DMD c.10087-2A>G Pathogenic/Likely pathogenic ★★ same type
DMD c.10223+1G>A Pathogenic ★★ same type
DMD c.10223+1G>C Pathogenic ★★ same type

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-cys3337ser (accessed [today's date]).

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