Is DMD p.Asp165Tyr (c.493G>T) pathogenic?

DMD p.Asp165Tyr (c.493G>T) is classified Uncertain significance in DMD (ClinVar, Multiple submitters, 2 submitters; last evaluated 2021-11-15). AlphaMissense: likely pathogenic (0.8471); Absent from gnomAD v4.1.

How common is DMD p.Asp165Tyr (c.493G>T) in the general population?

DMD p.Asp165Tyr (c.493G>T) is absent from gnomAD v4.1 (gnomAD).

What do computational predictors say about DMD p.Asp165Tyr (c.493G>T)?

AlphaMissense predicts likely pathogenic (score 0.8471) — an in-silico prediction, not a clinical call.

DMD p.Asp165Tyr

c.493G>T · rs1569528100 · VCV596419

Uncertain significance Multiple submitters

Classification

Uncertain significance

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 2 submitters

AlphaMissense

likely pathogenic

0.8471 · ACMG-weighted

gnomAD v4.1

Absent

absent from gnomAD v4.1

Missense predictors

2/2 damaging

AlphaMissense, REVEL

Computational evidence

Protein change
AlphaMissense	0.8471	likely pathogenic
REVEL	0.966	strongly pathogenic-leaning
⇒ AlphaMissense and REVEL both call this damaging.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 7.6	GERP 2.4, phastCons 1
Regional constraint	o/e 1.36	unconstrained · MANE · 1,863 kb · p 2.4e-62 · regional, not allelic
Overall
CADD	28.3	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 and SaProt are independent agreement signals.

Population frequency

gnomAD v4.1 · exomes + genomes

Absent from gnomAD v4.1. Not observed in any sequenced alleles — a rarity signal (ACMG PM2-supporting), not evidence of pathogenicity on its own.

Variant & gene context

Gene: DMD
Protein: p.Asp165Tyr
Coding: c.493G>T
MANE Select: NM_004006
dbSNP: rs1569528100
Type: single nucleotide variant
Location: chrX:32816505 (GRCh38)
Residue 165: the calponin-homology (ch) 2 domain; the 'actin-binding' region; a UniProt-annotated variant site (in one patient with becker muscular dystrophy)

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

Similar variants

DMD p.Asp165Val Uncertain significance ★ ⚠ same residue
DMD p.Asp165fs Pathogenic ★ 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-asp165tyr (accessed [today's date]).

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