Is DMD p.Ala2999Pro (c.8995G>C) pathogenic?

DMD p.Ala2999Pro (c.8995G>C) is classified Uncertain significance in DMD (ClinVar, Single submitter, 1 submitter; last evaluated 2024-08-27). AlphaMissense: likely pathogenic (0.8267); Absent from gnomAD v4.1; Associated with Cardiovascular phenotype.

What condition is associated with DMD p.Ala2999Pro (c.8995G>C)?

DMD p.Ala2999Pro (c.8995G>C) is associated with Cardiovascular phenotype (ClinVar).

How common is DMD p.Ala2999Pro (c.8995G>C) in the general population?

DMD p.Ala2999Pro (c.8995G>C) is absent from gnomAD v4.1 (gnomAD).

What do computational predictors say about DMD p.Ala2999Pro (c.8995G>C)?

AlphaMissense predicts likely pathogenic (score 0.8267) — an in-silico prediction, not a clinical call.

DMD p.Ala2999Pro

c.8995G>C · VCV3502581

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely pathogenic

0.8267 · ACMG-weighted

gnomAD v4.1

Absent

absent from gnomAD v4.1

Conditions

Cardiovascular phenotype

Computational evidence

Protein change
AlphaMissense	0.8267	likely pathogenic
REVEL	0.627	indeterminate
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 6	GERP 0.84, phastCons 1
Regional constraint	o/e 1.36	unconstrained · MANE · 1,863 kb · p 2.4e-62 · regional, not allelic
Overall
CADD	25.0	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

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.Ala2999Pro
Coding: c.8995G>C
MANE Select: NM_004006
Type: single nucleotide variant
Location: chrX:31444570 (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

Similar variants

DMD p.Ala2999Val Conflicting classifications of pathogenicity ★ ⚠ same residue
DMD p.Ala2999= Likely benign ★ same residue
DMD c.2804-2A>C Pathogenic/Likely pathogenic ★★ same condition
DMD c.31+1G>C Pathogenic ★★ same condition
DMD c.3432+2036A>G Pathogenic/Likely pathogenic ★★ same condition
DMD c.3433-1G>A Pathogenic ★★ same condition
DMD c.357+1G>T Pathogenic ★★ same condition
DMD c.9974+1G>A 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-ala2999pro (accessed [today's date]).

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