Is DMD p.Arg550Ser (c.1648C>A) pathogenic?

DMD p.Arg550Ser (c.1648C>A) is classified Uncertain significance in DMD (ClinVar, Single submitter, 1 submitter; last evaluated 2019-12-30). AlphaMissense: likely pathogenic (0.7601); Very rare (popmax 0.000165%); Associated with Cardiovascular phenotype.

What condition is associated with DMD p.Arg550Ser (c.1648C>A)?

DMD p.Arg550Ser (c.1648C>A) is associated with Cardiovascular phenotype (ClinVar).

How common is DMD p.Arg550Ser (c.1648C>A) in the general population?

DMD p.Arg550Ser (c.1648C>A) is very rare (popmax 0.000165%) (gnomAD).

What do computational predictors say about DMD p.Arg550Ser (c.1648C>A)?

AlphaMissense predicts likely pathogenic (score 0.7601) — an in-silico prediction, not a clinical call.

DMD p.Arg550Ser

c.1648C>A · rs778354538 · VCV1777185

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely pathogenic

0.7601 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 0.000165%)

Missense predictors

2/2 damaging

AlphaMissense, REVEL · SaProt no call

Conditions

Cardiovascular phenotype

Computational evidence

Protein change
AlphaMissense	0.7601	likely pathogenic
REVEL	0.815	moderately pathogenic-leaning
SaProt	—	not scored · why
⇒ AlphaMissense and REVEL both call this damaging; SaProt makes no call.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 12	GERP 1.9, phastCons 1
Regional constraint	o/e 1.36	unconstrained · MANE · 1,863 kb · p 2.4e-62 · regional, not allelic
Overall
CADD	26.0	PHRED · no single calibrated threshold — expert panels disagree

ClinVar classifies this uncertain; the computational predictors unanimously lean damaging — 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 0.000165%

Overall 0.000165% 2/1,211,238 alleles · very rare exomes 2/1,097,755 · genomes 0/113,483 · 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.Arg550Ser
Coding: c.1648C>A
MANE Select: NM_004006
dbSNP: rs778354538
Type: single nucleotide variant
Location: chrX:32573801 (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

Similar variants

DMD p.Arg550His Uncertain significance ★★ ⚠ same residue
DMD p.Arg550Cys Uncertain significance ★★ ⚠ same residue
DMD p.Arg550Pro Uncertain significance ★ ⚠ same residue
DMD c.2804-2A>C Pathogenic/Likely pathogenic ★★ same condition
DMD c.31+1G>C Pathogenic ★★ same condition
DMD c.3432+2036A>G Pathogenic/Likely pathogenic ★★ same condition
DMD c.3433-1G>A Pathogenic ★★ same condition
DMD c.357+1G>T 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-arg550ser (accessed [today's date]).

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