Is DHDDS p.Pro128fs (c.374_377dup) pathogenic?

DHDDS p.Pro128fs (c.374377dup) is classified Pathogenic in DHDDS (ClinVar, Single submitter, 1 submitter; last evaluated 2020-02-29). Absent from gnomAD; Associated with retinitis pigmentosa 59.

What condition is associated with DHDDS p.Pro128fs (c.374_377dup)?

DHDDS p.Pro128fs (c.374_377dup) is associated with retinitis pigmentosa 59 (ClinVar).

How common is DHDDS p.Pro128fs (c.374_377dup) in the general population?

DHDDS p.Pro128fs (c.374_377dup) is absent from gnomAD (gnomAD).

DHDDS p.Pro128fs

c.374_377dup · rs2124425894 · VCV1076541

Pathogenic Single submitter

Classification

Pathogenic

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

Consequence

frameshift

predicted LoF

gnomAD v4.1

Not reported

no gnomAD frequency available for this variant

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	predicted	premature termination codon in exon 5 of 9
Splicing
SpliceAI	—	not assessed · substitutions only
Constraint at this position
Conservation	phyloP 2.7	GERP 1.1, phastCons 1

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

Population frequency

dbSNP / gnomAD

No gnomAD frequency available for this variant. This is missing data, not an absence: the variant may or may not be present in gnomAD. Rarity (ACMG PM2) and BA1/BS1 cannot be assessed for it.

Variant & gene context

Gene: DHDDS
Protein: p.Pro128fs
Coding: c.374_377dup
MANE Select: NM_205861
dbSNP: rs2124425894
Type: Duplication
Location: chr1:26446365 (GRCh38)
Gene constraint: LOEUF 0.536 · pLI 0.91 (gnomAD)
Structure: AlphaFold pLDDT 95.01 · 9 PDB
Residue 128: 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 p.Pro128= Likely benign ★ same residue
DHDDS p.Val173fs Pathogenic/Likely pathogenic ★★ same condition
DHDDS p.Trp171fs Pathogenic ★ same condition
DHDDS c.180+6dup Likely benign ★ same condition
DHDDS c.658-11_658-9dup Likely benign ★ same condition
DHDDS c.766-6dup Likely benign ★ same condition
DHDDS c.658-2A>G Likely pathogenic ★★ same condition
DHDDS p.Arg205Gln 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-pro128fs (accessed [today's date]).

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