Is DMD p.Thr511Ile (c.1532C>T) pathogenic?

DMD p.Thr511Ile (c.1532C>T) is classified Uncertain significance in DMD (ClinVar, Single submitter, 2 submitters; last evaluated 2021-09-02). AlphaMissense: likely pathogenic (0.9577); Very rare (popmax 0.000338%, nfe); Associated with Duchenne muscular dystrophy.

What condition is associated with DMD p.Thr511Ile (c.1532C>T)?

DMD p.Thr511Ile (c.1532C>T) is associated with Duchenne muscular dystrophy, cardiomyopathy, Becker muscular dystrophy (ClinVar).

How common is DMD p.Thr511Ile (c.1532C>T) in the general population?

DMD p.Thr511Ile (c.1532C>T) is very rare (popmax 0.000338%, nfe) (gnomAD).

How is Duchenne muscular dystrophy inherited?

Typically X-linked recessive (Orphanet). A genetic counselor can assess individual risk for a family.

What do computational predictors say about DMD p.Thr511Ile (c.1532C>T)?

AlphaMissense predicts likely pathogenic (score 0.9577) — an in-silico prediction, not a clinical call.

DMD p.Thr511Ile

c.1532C>T · rs1295185756 · VCV864442

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 2 submitters

AlphaMissense

likely pathogenic

0.9577 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 0.000338%, nfe)

Conditions

Duchenne muscular dystrophy

Computational evidence

Protein change
AlphaMissense	0.9577	likely pathogenic · top 8% in DMD
REVEL	0.451	indeterminate
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 1.7, phastCons 1
Regional constraint	o/e 1.36	unconstrained · MANE · 1,863 kb · p 2.4e-62 · regional, not allelic
Overall
CADD	25.1	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 0.000338% European (non-Finnish) · 3/887,006 alleles

Filtering AF 9e-05% ClinGen BA1/BS1 input FAF95, joint · FAF99 2.5e-05%

Overall 0.000333% 4/1,202,568 alleles · very rare exomes 4/1,088,768 · genomes 0/113,800 · joint denominator

Ancestry group	Frequency	1 in
Remaining individualsnot grpmax-eligible	0.00211%	47,352
European (non-Finnish)grpmax	0.000338%	295,669

Remaining individuals shows a higher raw frequency than the grpmax group above it. gnomAD excludes bottlenecked groups — Finnish, Ashkenazi Jewish, Amish and “Remaining individuals” — from grpmax, because founder effects make their frequencies unrepresentative for filtering. The table is sorted by frequency, so an excluded group can sit above the grpmax row.

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.Thr511Ile
Coding: c.1532C>T
MANE Select: NM_004006
dbSNP: rs1295185756
Type: single nucleotide variant
Location: chrX:32595827 (GRCh38)
Residue 511: a UniProt-annotated variant site (in bmd)

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

Disease context

Duchenne muscular dystrophy — disease report on Sugi Atlas → Associated genes, phenotypes, clinical trials & treatments

Also linked: cardiomyopathy Becker muscular dystrophy

For Duchenne muscular dystrophy (Orphanet):

Inheritance: X-linked recessive
Onset: Childhood
Prevalence: 1-9 / 100 000 (Worldwide)

Similar variants

DMD p.Thr511Ser 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-thr511ile (accessed [today's date]).

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