Is DHDDS p.Ser332Ter (c.995C>G) pathogenic?

DHDDS p.Ser332Ter (c.995C>G) is classified Uncertain significance in DHDDS (ClinVar, Multiple submitters, 3 submitters; last evaluated 2025-09-10). Ultra-rare (popmax 0.0622%, mid); Associated with retinitis pigmentosa 59.

What condition is associated with DHDDS p.Ser332Ter (c.995C>G)?

DHDDS p.Ser332Ter (c.995C>G) is associated with retinitis pigmentosa 59 (ClinVar).

How common is DHDDS p.Ser332Ter (c.995C>G) in the general population?

DHDDS p.Ser332Ter (c.995C>G) is ultra-rare (popmax 0.0622%, mid) (gnomAD).

DHDDS p.Ser332Ter

c.995C>G · rs770732789 · VCV2150050

Uncertain significance Multiple submitters

Classification

Uncertain significance

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 3 submitters

Consequence

nonsense (stop-gain)

predicted LoF

gnomAD v4.1

Rare

ultra-rare (popmax 0.0622%, mid)

Conditions

retinitis pigmentosa 59

Computational evidence

Protein change
Missense predictors do not apply to this variant type; conservation carries the signal.
Consequence	nonsense (stop-gain)	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 · no allele here is in the release
Constraint at this position
Conservation	phyloP 5.9	GERP 0.72, phastCons 1
Overall
CADD	37.0	PHRED · no single calibrated threshold — expert panels disagree

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

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.0622% Middle Eastern · 3/4,820 alleles

Filtering AF 0.0169% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.00901%

Overall 0.00062% 10/1,611,788 alleles · ultra-rare

Ancestry group	Frequency	1 in
Middle Easterngrpmax	0.0622%	1,607
Admixed American	0.00167%	60,006
Remaining individualsnot grpmax-eligible	0.0016%	62,346
African / African-American	0.00133%	74,908
European (non-Finnish)	0.000339%	295,011

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.Ser332Ter
Coding: c.995C>G
MANE Select: NM_205861
dbSNP: rs770732789
Type: single nucleotide variant
Location: chr1:26469124 (GRCh38)
Gene constraint: LOEUF 0.536 · pLI 0.91 (gnomAD)
Structure: AlphaFold pLDDT 95.01 · 9 PDB
Residue 332: 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

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-ser332ter (accessed [today's date]).

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