Is DMD p.Ala3109Ser (c.9325G>T) pathogenic?

DMD p.Ala3109Ser (c.9325G>T) is classified Conflicting classifications of pathogenicity in DMD (ClinVar, Conflicting submitters, 5 submitters; last evaluated 2025-12-27). AlphaMissense: ambiguous (0.4581); Ultra-rare (popmax 0.0168%, nfe); Associated with Cardiovascular phenotype.

What condition is associated with DMD p.Ala3109Ser (c.9325G>T)?

DMD p.Ala3109Ser (c.9325G>T) is associated with Cardiovascular phenotype, cardiomyopathy, Becker muscular dystrophy (ClinVar).

How common is DMD p.Ala3109Ser (c.9325G>T) in the general population?

DMD p.Ala3109Ser (c.9325G>T) is ultra-rare (popmax 0.0168%, nfe) (gnomAD).

What do computational predictors say about DMD p.Ala3109Ser (c.9325G>T)?

AlphaMissense predicts ambiguous (score 0.4581) — an in-silico prediction, not a clinical call.

DMD p.Ala3109Ser

c.9325G>T · rs201718067 · VCV239613

Conflicting classifications of pathogenicity Conflicting submitters

Classification

Conflicting classifications of pathogenicity

ClinVar

Review

Conflicting submitters ★☆☆☆

ClinVar · 5 submitters

AlphaMissense

ambiguous

0.4581 · ACMG-weighted

gnomAD v4.1

Rare

ultra-rare (popmax 0.0168%, nfe)

Conditions

Cardiovascular phenotype

Computational evidence

Protein change
AlphaMissense	0.4581	ambiguous
REVEL	0.47	indeterminate
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 7.7	GERP 3.4, phastCons 1
Regional constraint	o/e 0.66	unconstrained · MANE · 170 kb · p 2.6e-08 · regional, not allelic
Overall
CADD	26.3	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 0.0168% European (non-Finnish) · 150/894,786 alleles

Filtering AF 0.0146% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.0137%

Overall 0.0128% 155/1,209,508 alleles · ultra-rare

Ancestry group	Frequency	1 in
European (non-Finnish)grpmax	0.0168%	5,965
Remaining individualsnot grpmax-eligible	0.0042%	23,792
African / African-American	0.0035%	28,598
Finnishnot grpmax-eligible	0.00215%	46,566

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.Ala3109Ser
Coding: c.9325G>T
MANE Select: NM_004006
dbSNP: rs201718067
Type: single nucleotide variant
Location: chrX:31223083 (GRCh38)
Residue 3109: an α-helix; the 'interaction with synm' 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: cardiomyopathy Becker muscular dystrophy Duchenne muscular dystrophy

Similar variants

DMD p.Ala3109fs Pathogenic ★ 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
DMD c.10223+1G>C Pathogenic ★★ same condition
DMD c.10224-2A>G 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-ala3109ser (accessed [today's date]).

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