Is DMD p.Pro857Ser (c.2569C>T) pathogenic?

DMD p.Pro857Ser (c.2569C>T) is classified Benign/Likely benign in DMD (ClinVar, Multiple submitters, 9 submitters; last evaluated 2026-02-01). AlphaMissense: likely benign (0.0825); Rare (popmax 0.936%, sas); Associated with Cardiovascular phenotype.

What condition is associated with DMD p.Pro857Ser (c.2569C>T)?

DMD p.Pro857Ser (c.2569C>T) is associated with Cardiovascular phenotype, cardiomyopathy, Becker muscular dystrophy (ClinVar).

How common is DMD p.Pro857Ser (c.2569C>T) in the general population?

DMD p.Pro857Ser (c.2569C>T) is rare (popmax 0.936%, sas) (gnomAD).

What do computational predictors say about DMD p.Pro857Ser (c.2569C>T)?

AlphaMissense predicts likely benign (score 0.0825) — an in-silico prediction, not a clinical call.

DMD p.Pro857Ser

c.2569C>T · rs552275776 · VCV227307

Benign/Likely benign Multiple submitters

Classification

Benign/Likely benign

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 9 submitters

AlphaMissense

likely benign

0.0825 · ACMG-weighted

gnomAD v4.1

Rare

rare (popmax 0.936%, sas)

Missense predictors

0/2 damaging

AlphaMissense, REVEL

Conditions

Cardiovascular phenotype

Computational evidence

Protein change
AlphaMissense	0.0825	likely benign
REVEL	0.051	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 7	GERP 0.54, phastCons 1
Regional constraint	o/e 1.36	unconstrained · MANE · 1,863 kb · p 2.4e-62 · regional, not allelic
Overall
CADD	16.84	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 0.936% South Asian · 532/56,824 alleles

Filtering AF 0.87% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.844%

Overall 0.0461% 558/1,209,669 alleles · rare

Ancestry group	Frequency	1 in
South Asiangrpmax	0.936%	107
Middle Eastern	0.138%	725
Remaining individualsnot grpmax-eligible	0.0378%	2,644
East Asian	0.00296%	33,756
European (non-Finnish)	0.000112%	895,007

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.Pro857Ser
Coding: c.2569C>T
MANE Select: NM_004006
dbSNP: rs552275776
Type: single nucleotide variant
Location: chrX:32491330 (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.Pro857= Likely benign ★★ same residue
DMD p.Pro857Leu 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

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-pro857ser (accessed [today's date]).

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