Is DMD p.Pro292Ser (c.874C>T) pathogenic?

DMD p.Pro292Ser (c.874C>T) is classified Uncertain significance in DMD (ClinVar, Multiple submitters, 2 submitters; last evaluated 2023-12-16). AlphaMissense: likely benign (0.0962); Very rare (popmax 0.000112%, nfe); Associated with DMD-related disorder.

What condition is associated with DMD p.Pro292Ser (c.874C>T)?

DMD p.Pro292Ser (c.874C>T) is associated with DMD-related disorder, Duchenne muscular dystrophy (ClinVar).

How common is DMD p.Pro292Ser (c.874C>T) in the general population?

DMD p.Pro292Ser (c.874C>T) is very rare (popmax 0.000112%, nfe) (gnomAD).

What do computational predictors say about DMD p.Pro292Ser (c.874C>T)?

AlphaMissense predicts likely benign (score 0.0962) — an in-silico prediction, not a clinical call.

DMD p.Pro292Ser

c.874C>T · rs2521103102 · VCV2107099

Uncertain significance Multiple submitters

Classification

Uncertain significance

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 2 submitters

AlphaMissense

likely benign

0.0962 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 0.000112%, nfe)

Missense predictors

0/2 damaging

AlphaMissense, REVEL · SaProt no call

Conditions

DMD-related disorder

Computational evidence

Protein change
AlphaMissense	0.0962	likely benign
REVEL	0.094	moderately benign-leaning
SaProt	—	not scored · why
⇒ AlphaMissense and REVEL both call this tolerated; SaProt makes no call.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 7.9	GERP 1.2, phastCons 1
Regional constraint	o/e 1.36	unconstrained · MANE · 1,863 kb · p 2.4e-62 · regional, not allelic
Overall
CADD	20.3	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 is an independent agreement signal.

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.000112% European (non-Finnish) · 1/891,847 alleles

Overall 8.3e-05% 1/1,204,538 alleles · very rare exomes 1/1,091,869 · genomes 0/112,669 · 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.Pro292Ser
Coding: c.874C>T
MANE Select: NM_004006
dbSNP: rs2521103102
Type: single nucleotide variant
Location: chrX:32697956 (GRCh38)

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

Disease context

DMD-related disorder

Also linked: Duchenne muscular dystrophy

Similar variants

DMD p.Pro292Arg Uncertain significance ★★ ⚠ same residue
DMD p.Pro292= Likely benign ★★ same residue
DMD p.Pro292fs Pathogenic ★ 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

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-pro292ser (accessed [today's date]).

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