Is DMD p.Cys650Tyr (c.1949G>A) pathogenic?

DMD p.Cys650Tyr (c.1949G>A) is classified Likely benign in DMD (ClinVar, Single submitter, 1 submitter; last evaluated 2025-09-17). AlphaMissense: likely benign (0.0874); Very rare (popmax 0.00173%, afr).

How common is DMD p.Cys650Tyr (c.1949G>A) in the general population?

DMD p.Cys650Tyr (c.1949G>A) is very rare (popmax 0.00173%, afr) (gnomAD).

What do computational predictors say about DMD p.Cys650Tyr (c.1949G>A)?

AlphaMissense predicts likely benign (score 0.0874) — an in-silico prediction, not a clinical call.

DMD p.Cys650Tyr

c.1949G>A · VCV4684514

Likely benign Single submitter

Classification

Likely benign

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.0874 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 0.00173%, afr)

Missense predictors

0/2 damaging

AlphaMissense, REVEL

Computational evidence

Protein change
AlphaMissense	0.0874	likely benign
REVEL	0.035	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 3.3	GERP -0.061, phastCons 1
Regional constraint	o/e 1.36	unconstrained · MANE · 1,863 kb · p 2.4e-62 · regional, not allelic
Overall
CADD	20.2	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 0.00173% African / African-American · 1/57,802 alleles

Overall 9.11e-05% 1/1,098,112 alleles · very rare

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.Cys650Tyr
Coding: c.1949G>A
MANE Select: NM_004006
Type: single nucleotide variant
Location: chrX:32565745 (GRCh38)

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

Similar variants

DMD p.Cys650Ter Likely pathogenic ★ same residue
DMD p.Cys650Phe Uncertain significance ★ ⚠ same residue
DMD c.10086+1G>A Pathogenic ★★ same type
DMD c.10086+1G>T Pathogenic ★★ same type
DMD c.10086+2T>C Pathogenic ★★ same type
DMD c.10087-2A>G Pathogenic/Likely pathogenic ★★ same type
DMD c.10223+1G>A Pathogenic ★★ same type
DMD c.10223+1G>C Pathogenic ★★ same type

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-cys650tyr (accessed [today's date]).

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