Is DHDDS p.Thr330= (c.990T>C) pathogenic?

DHDDS p.Thr330= (c.990T>C) is classified Conflicting classifications of pathogenicity in DHDDS (ClinVar, Conflicting submitters, 4 submitters; last evaluated 2026-01-18). Ultra-rare (popmax 0.0417%, amr); Associated with retinitis pigmentosa 59.

What condition is associated with DHDDS p.Thr330= (c.990T>C)?

DHDDS p.Thr330= (c.990T>C) is associated with retinitis pigmentosa 59, retinitis pigmentosa (ClinVar).

How common is DHDDS p.Thr330= (c.990T>C) in the general population?

DHDDS p.Thr330= (c.990T>C) is ultra-rare (popmax 0.0417%, amr) (gnomAD).

DHDDS p.Thr330=

c.990T>C · rs773902080 · VCV297079

Conflicting classifications of pathogenicity Conflicting submitters

Classification

Conflicting classifications of pathogenicity

ClinVar

Review

Conflicting submitters ★☆☆☆

ClinVar · 4 submitters

gnomAD v4.1

Rare

ultra-rare (popmax 0.0417%, amr)

Conditions

retinitis pigmentosa 59

Computational evidence

Protein change
Missense predictors do not apply to this variant type; conservation carries the signal.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP -1.5	GERP -1.6
Overall
CADD	5.968	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.0417% Admixed American · 25/60,008 alleles

Filtering AF 0.0289% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.0247%

Overall 0.0164% 265/1,611,882 alleles · ultra-rare

Ancestry group	Frequency	1 in
Admixed Americangrpmax	0.0417%	2,400
European (non-Finnish)	0.0196%	5,108
Remaining individualsnot grpmax-eligible	0.00802%	12,470
Ashkenazi Jewishnot grpmax-eligible	0.00338%	29,606
African / African-American	0.00267%	37,452
South Asian	0.0011%	91,012

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.Thr330=
Coding: c.990T>C
MANE Select: NM_205861
dbSNP: rs773902080
Type: single nucleotide variant
Location: chr1:26469119 (GRCh38)
Gene constraint: LOEUF 0.536 · pLI 0.91 (gnomAD)
Structure: AlphaFold pLDDT 95.01 · 9 PDB
Residue 330: a UniProt-annotated variant site (in rp59; in a patient with congenital disorder of glycosylation)

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

Also linked: retinitis pigmentosa

Similar variants

DHDDS p.Thr330Asn 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
DHDDS p.Gly35Glu Pathogenic/Likely 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-thr330 (accessed [today's date]).

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