Is DHDDS p.Tyr76= (c.228C>T) pathogenic?

DHDDS p.Tyr76= (c.228C>T) is classified Likely benign in DHDDS (ClinVar, Multiple submitters, 2 submitters; last evaluated 2024-02-05). Very rare (popmax 0.00668%, eas); Associated with retinitis pigmentosa 59.

What condition is associated with DHDDS p.Tyr76= (c.228C>T)?

DHDDS p.Tyr76= (c.228C>T) is associated with retinitis pigmentosa 59 (ClinVar).

How common is DHDDS p.Tyr76= (c.228C>T) in the general population?

DHDDS p.Tyr76= (c.228C>T) is very rare (popmax 0.00668%, eas) (gnomAD).

DHDDS p.Tyr76=

c.228C>T · rs566029202 · VCV763963

Likely benign Multiple submitters

Classification

Likely benign

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 2 submitters

gnomAD v4.1

Rare

very rare (popmax 0.00668%, eas)

Conditions

retinitis pigmentosa 59

Computational evidence

Protein change
Missense predictors do not apply to this variant type; conservation carries the signal.
Splicing
SpliceAI	<0.2	all four deltas below 0.2 · C>G here scores Δ0.20 · evaluated, not missing
Constraint at this position
Conservation	phyloP -2.8	GERP -3.4
Overall
CADD	11.84	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.00668% East Asian · 3/44,884 alleles

Filtering AF 0.00177% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.00123%

Overall 0.0018% 29/1,614,144 alleles · very rare

Ancestry group	Frequency	1 in
East Asiangrpmax	0.00668%	14,961
European (non-Finnish)	0.00212%	47,201
Remaining individualsnot grpmax-eligible	0.0016%	62,506

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.Tyr76=
Coding: c.228C>T
MANE Select: NM_205861
dbSNP: rs566029202
Type: single nucleotide variant
Location: chr1:26442778 (GRCh38)
Gene constraint: LOEUF 0.536 · pLI 0.91 (gnomAD)
Structure: AlphaFold pLDDT 95.01 · 9 PDB
Residue 76: a UniProt-annotated variant site (in rp59; in a patient with congenital disorder of glycosylation); a β-strand

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 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
DHDDS p.Gly35Glu Pathogenic/Likely pathogenic ★★ same condition
DHDDS p.Lys42Glu 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-tyr76 (accessed [today's date]).

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