Is DMD p.Ala2020Pro (c.6058G>C) pathogenic?

DMD p.Ala2020Pro (c.6058G>C) is classified Likely benign in DMD (ClinVar, Multiple submitters, 4 submitters; last evaluated 2025-11-12). AlphaMissense: ambiguous (0.4948); Very rare (popmax 0.00548%, nfe); Associated with Cardiovascular phenotype.

What condition is associated with DMD p.Ala2020Pro (c.6058G>C)?

DMD p.Ala2020Pro (c.6058G>C) is associated with Cardiovascular phenotype, cardiomyopathy, Becker muscular dystrophy (ClinVar).

How common is DMD p.Ala2020Pro (c.6058G>C) in the general population?

DMD p.Ala2020Pro (c.6058G>C) is very rare (popmax 0.00548%, nfe) (gnomAD).

What do computational predictors say about DMD p.Ala2020Pro (c.6058G>C)?

AlphaMissense predicts ambiguous (score 0.4948) — an in-silico prediction, not a clinical call.

DMD p.Ala2020Pro

c.6058G>C · rs765460659 · VCV526101

Likely benign Multiple submitters

Classification

Likely benign

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 4 submitters

AlphaMissense

ambiguous

0.4948 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 0.00548%, nfe)

Conditions

Cardiovascular phenotype

Computational evidence

Protein change
AlphaMissense	0.4948	ambiguous
REVEL	0.11	moderately benign-leaning
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 0.39	GERP 1.1, phastCons 0.91
Regional constraint	o/e 1.36	unconstrained · MANE · 1,863 kb · p 2.4e-62 · regional, not allelic
Overall
CADD	21.2	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 0.00548% European (non-Finnish) · 49/893,584 alleles

Filtering AF 0.0042% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.00378%

Overall 0.00414% 50/1,207,753 alleles · very rare

Ancestry group	Frequency	1 in
European (non-Finnish)grpmax	0.00548%	18,236
Remaining individualsnot grpmax-eligible	0.00211%	47,484

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.Ala2020Pro
Coding: c.6058G>C
MANE Select: NM_004006
dbSNP: rs765460659
Type: single nucleotide variant
Location: chrX:32310141 (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.Ala2020Ser Uncertain significance ★★ ⚠ 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-ala2020pro (accessed [today's date]).

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