Is DMD p.Pro3417Ala (c.10249C>G) pathogenic?

DMD p.Pro3417Ala (c.10249C>G) is classified Conflicting classifications of pathogenicity in DMD (ClinVar, Conflicting submitters, 10 submitters; last evaluated 2026-01-07). AlphaMissense: ambiguous (0.3482); Ultra-rare (popmax 0.0127%, nfe); Associated with Cardiovascular phenotype.

What condition is associated with DMD p.Pro3417Ala (c.10249C>G)?

DMD p.Pro3417Ala (c.10249C>G) is associated with Cardiovascular phenotype, cardiomyopathy, Becker muscular dystrophy (ClinVar).

How common is DMD p.Pro3417Ala (c.10249C>G) in the general population?

DMD p.Pro3417Ala (c.10249C>G) is ultra-rare (popmax 0.0127%, nfe) (gnomAD).

What do computational predictors say about DMD p.Pro3417Ala (c.10249C>G)?

AlphaMissense predicts ambiguous (score 0.3482) — an in-silico prediction, not a clinical call.

DMD p.Pro3417Ala

c.10249C>G · rs373898385 · VCV452134

Conflicting classifications of pathogenicity Conflicting submitters

Classification

Conflicting classifications of pathogenicity

ClinVar

Review

Conflicting submitters ★☆☆☆

ClinVar · 10 submitters

AlphaMissense

ambiguous

0.3482 · ACMG-weighted

gnomAD v4.1

Rare

ultra-rare (popmax 0.0127%, nfe)

Conditions

Cardiovascular phenotype

Computational evidence

Protein change
AlphaMissense	0.3482	ambiguous
REVEL	0.717	pathogenic-leaning
SaProt	—	not scored · why
Splicing
SpliceAI	<0.2	no splice effect predicted · four deltas, not one · how we know
Constraint at this position
Conservation	phyloP 12	GERP 3.4, phastCons 1
Regional constraint	o/e 1.19	unconstrained · MANE · 6,307 bp · p 0.21 · regional, not allelic
Overall
CADD	24.5	PHRED · no single calibrated threshold — expert panels disagree

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

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.0127% European (non-Finnish) · 113/892,648 alleles

Filtering AF 0.0107% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.01%

Overall 0.00995% 120/1,205,988 alleles · ultra-rare exomes 112/1,094,602 · genomes 8/111,386 · joint denominator

Ancestry group	Frequency	1 in
European (non-Finnish)grpmax	0.0127%	7,900
African / African-American	0.00701%	14,256
Remaining individualsnot grpmax-eligible	0.00632%	15,833

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.Pro3417Ala
Coding: c.10249C>G
MANE Select: NM_004006
dbSNP: rs373898385
Type: single nucleotide variant
Location: chrX:31177945 (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.Pro3417= 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
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-pro3417ala (accessed [today's date]).

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