Is DHDDS p.Thr276fs (c.827_828del) pathogenic?

DHDDS p.Thr276fs (c.827828del) is classified Likely pathogenic in DHDDS (ClinVar, Single submitter, 1 submitter; last evaluated 2025-09-24). Associated with retinitis pigmentosa 59.

What condition is associated with DHDDS p.Thr276fs (c.827_828del)?

DHDDS p.Thr276fs (c.827_828del) is associated with retinitis pigmentosa 59 (ClinVar).

DHDDS p.Thr276fs

c.827_828del · VCV4816176

Likely pathogenic Single submitter

Classification

Likely pathogenic

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

Consequence

frameshift

predicted LoF

gnomAD v4.1

Rare

Conditions

retinitis pigmentosa 59

Computational evidence

Protein change
Missense predictors do not apply to this variant type; conservation carries the signal.
Consequence	frameshift	predicted loss-of-function in a LoF-intolerant gene
NMD	escapes	premature termination codon in the last exon (9 of 9) — the truncated protein is likely expressed. PVS1 input, not an applied code
Splicing
SpliceAI	—	not assessed · substitutions only
Constraint at this position
Conservation	phyloP -0.12	GERP -0.47, phastCons 0.77

Predicted loss-of-function is descriptive, not an applied PVS1 code.

Variant & gene context

Gene: DHDDS
Protein: p.Thr276fs
Coding: c.827_828del
MANE Select: NM_205861
Type: Deletion
Location: chr1:26468955 (GRCh38)
Gene constraint: LOEUF 0.536 · pLI 0.91 (gnomAD)
Structure: AlphaFold pLDDT 95.01 · 9 PDB
Residue 276: 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

retinitis pigmentosa 59 — disease report on Sugi Atlas → Associated genes, phenotypes, clinical trials & treatments

Similar variants

DHDDS p.His222fs Likely pathogenic ★★ same condition
DHDDS p.Ser88fs Pathogenic/Likely pathogenic ★★ same condition
DHDDS c.650_657+54del Likely pathogenic ★ same condition
DHDDS p.Asp34fs Pathogenic ★ same condition
DHDDS p.Phe215fs Likely pathogenic ★ same condition
DHDDS c.323+2_323+5del Conflicting classifications of pathogenicity ★ ⚠ same condition
DHDDS c.766-4del Uncertain significance ★ same condition
DHDDS p.Arg258fs Uncertain significance ★ 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-thr276fs (accessed [today's date]).

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