Is DMD p.Ala528Val (c.1583C>T) pathogenic?

DMD p.Ala528Val (c.1583C>T) is classified Uncertain significance in DMD (ClinVar, Single submitter, 1 submitter; last evaluated 2018-01-01). AlphaMissense: likely benign (0.0947); Very rare (popmax 0.000112%, nfe).

How common is DMD p.Ala528Val (c.1583C>T) in the general population?

DMD p.Ala528Val (c.1583C>T) is very rare (popmax 0.000112%, nfe) (gnomAD).

What do computational predictors say about DMD p.Ala528Val (c.1583C>T)?

AlphaMissense predicts likely benign (score 0.0947) — an in-silico prediction, not a clinical call.

DMD p.Ala528Val

c.1583C>T · rs753624531 · VCV810558

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.0947 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 0.000112%, nfe)

Missense predictors

0/2 damaging

AlphaMissense, REVEL

Computational evidence

Protein change
AlphaMissense	0.0947	likely benign
REVEL	0.11	moderately benign-leaning
⇒ AlphaMissense and REVEL both call this tolerated.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 6.3	GERP -0.74, phastCons 1
Regional constraint	o/e 1.36	unconstrained · MANE · 1,863 kb · p 2.4e-62 · regional, not allelic
Overall
CADD	21.9	PHRED · no single calibrated threshold — expert panels disagree

ClinVar classifies this uncertain; the computational predictors unanimously lean tolerated — a triage signal, not a reclassification

AlphaMissense carries the ACMG weight for missense; REVEL and SaProt are independent agreement signals.

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.000112% European (non-Finnish) · 1/894,497 alleles

Overall 9.12e-05% 1/1,096,968 alleles · very rare

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.Ala528Val
Coding: c.1583C>T
MANE Select: NM_004006
dbSNP: rs753624531
Type: single nucleotide variant
Location: chrX:32595776 (GRCh38)
Residue 528: a UniProt-annotated variant site (in bmd)

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

Similar variants

DMD p.Ala528Ser Uncertain significance ★ ⚠ same residue
DMD p.Ala528Thr Conflicting classifications of pathogenicity ★ ⚠ same residue
DMD p.Ala528= Likely benign 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

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-ala528val (accessed [today's date]).

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