Is DHDDS p.Asp273Tyr (c.817G>T) pathogenic?

DHDDS p.Asp273Tyr (c.817G>T) is classified Uncertain significance in DHDDS (ClinVar, Multiple submitters, 2 submitters; last evaluated 2022-05-20). AlphaMissense: likely pathogenic (0.7129); Very rare (popmax 0.00223%, eas); Associated with developmental delay and seizures with or without movement abnormalities.

How common is DHDDS p.Asp273Tyr (c.817G>T) in the general population?

DHDDS p.Asp273Tyr (c.817G>T) is very rare (popmax 0.00223%, eas) (gnomAD).

What do computational predictors say about DHDDS p.Asp273Tyr (c.817G>T)?

AlphaMissense predicts likely pathogenic (score 0.7129) — an in-silico prediction, not a clinical call.

DHDDS p.Asp273Tyr

Q: What condition is associated with DHDDS p.Asp273Tyr (c.817G>T)?

DHDDS p.Asp273Tyr (c.817G>T) is associated with developmental delay and seizures with or without movement abnormalities, retinitis pigmentosa 59 (ClinVar).

c.817G>T · rs182263884 · VCV983319

Uncertain significance Multiple submitters

Classification

Uncertain significance

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 2 submitters

AlphaMissense

likely pathogenic

0.7129 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 0.00223%, eas)

Missense predictors

2/3 damaging

AlphaMissense, REVEL, SaProt

Conditions

developmental delay and seizures with or without movement abnormalities

Computational evidence

Protein change
AlphaMissense	0.7129	likely pathogenic
REVEL	0.288	benign-leaning
SaProt	LLR -11.97	damaging
⇒ AlphaMissense and SaProt call this damaging; REVEL does not.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 12	GERP 1.7, phastCons 1
Regional constraint	o/e 0.89	unconstrained · MANE · 26 kb · p 0.063 · regional, not allelic
Overall
CADD	28.5	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 0.00223% East Asian · 1/44,876 alleles

Overall 0.000656% 1/152,328 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: DHDDS
Protein: p.Asp273Tyr
Coding: c.817G>T
MANE Select: NM_205861
dbSNP: rs182263884
Type: single nucleotide variant
Location: chr1:26468946 (GRCh38)
Gene constraint: LOEUF 0.536 · pLI 0.91 (gnomAD)
Structure: AlphaFold pLDDT 95.01 · 9 PDB
Residue 273: a UniProt-annotated variant site (in rp59; in a patient with congenital disorder of glycosylation); an α-helix

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

Disease context

developmental delay and seizures with or without movement abnormalities — disease report on Sugi Atlas → Associated genes, phenotypes, clinical trials & treatments

Also linked: retinitis pigmentosa 59

Similar variants

DHDDS p.Asp273Asn Uncertain significance ★ ⚠ same residue
DHDDS p.Asp273Glu Uncertain significance ⚠ same residue
DHDDS c.658-2A>G Likely pathogenic ★★ same condition
DHDDS p.Arg205Gln Pathogenic ★★ same condition
DHDDS p.Arg211Gln Pathogenic ★★ same condition
DHDDS p.Arg37Cys Pathogenic ★★ same condition
DHDDS p.Arg37His Pathogenic/Likely pathogenic ★★ same condition
DHDDS p.Arg37Ser 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/dhdds-p-asp273tyr (accessed [today's date]).

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