Is DMD p.Pro257Ser (c.769C>T) pathogenic?

DMD p.Pro257Ser (c.769C>T) is classified Likely benign in DMD (ClinVar, Multiple submitters, 3 submitters; last evaluated 2025-06-22). AlphaMissense: likely benign (0.0792); Ultra-rare (popmax 0.0176%, amr); Associated with Cardiovascular phenotype.

What condition is associated with DMD p.Pro257Ser (c.769C>T)?

DMD p.Pro257Ser (c.769C>T) is associated with Cardiovascular phenotype, cardiomyopathy, Becker muscular dystrophy (ClinVar).

How common is DMD p.Pro257Ser (c.769C>T) in the general population?

DMD p.Pro257Ser (c.769C>T) is ultra-rare (popmax 0.0176%, amr) (gnomAD).

What do computational predictors say about DMD p.Pro257Ser (c.769C>T)?

AlphaMissense predicts likely benign (score 0.0792) — an in-silico prediction, not a clinical call.

DMD p.Pro257Ser

c.769C>T · rs1305908922 · VCV967332

Likely benign Multiple submitters

Classification

Likely benign

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 3 submitters

AlphaMissense

likely benign

0.0792 · ACMG-weighted

gnomAD v4.1

Rare

ultra-rare (popmax 0.0176%, amr)

Missense predictors

0/2 damaging

AlphaMissense, REVEL · SaProt no call

Conditions

Cardiovascular phenotype

Computational evidence

Protein change
AlphaMissense	0.0792	likely benign
REVEL	0.056	moderately benign-leaning
SaProt	—	not scored · why
⇒ AlphaMissense and REVEL both call this tolerated; SaProt makes no call.
Splicing
SpliceAI	<0.2	no splice effect predicted · four deltas, not one · how we know
Constraint at this position
Conservation	phyloP 2.1	GERP 3.9, phastCons 0.94
Regional constraint	o/e 1.36	unconstrained · MANE · 1,863 kb · p 2.4e-62 · regional, not allelic
Overall
CADD	11.95	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 0.0176% Admixed American · 8/45,570 alleles

Filtering AF 0.00872% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.00633%

Overall 0.000662% 8/1,208,125 alleles · ultra-rare exomes 7/1,096,683 · genomes 1/111,442 · joint denominator

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.Pro257Ser
Coding: c.769C>T
MANE Select: NM_004006
dbSNP: rs1305908922
Type: single nucleotide variant
Location: chrX:32699174 (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.Pro257= 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-pro257ser (accessed [today's date]).

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