Is DHDDS p.Asp34fs (c.100del) pathogenic?

DHDDS p.Asp34fs (c.100del) is classified Pathogenic in DHDDS (ClinVar, Single submitter, 1 submitter; last evaluated 2022-11-02). Very rare (popmax 0.00133%, afr); Associated with retinitis pigmentosa 59.

What condition is associated with DHDDS p.Asp34fs (c.100del)?

DHDDS p.Asp34fs (c.100del) is associated with retinitis pigmentosa 59 (ClinVar).

How common is DHDDS p.Asp34fs (c.100del) in the general population?

DHDDS p.Asp34fs (c.100del) is very rare (popmax 0.00133%, afr) (gnomAD).

DHDDS p.Asp34fs

c.100del · rs2075181080 · VCV2021747

Pathogenic Single submitter

Classification

Pathogenic

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

Consequence

frameshift

predicted LoF

gnomAD v4.1

Rare

very rare (popmax 0.00133%, afr)

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 3 of 9
Splicing
SpliceAI	—	not assessed · substitutions only
Constraint at this position
Conservation	phyloP 7.9	GERP 2, phastCons 1
Overall
CADD	35.0	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 0.00133% African / African-American · 1/74,942 alleles

Overall 6.2e-05% 1/1,613,924 alleles · very rare exomes 0/1,461,670 · genomes 1/152,254 · joint denominator

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.Asp34fs
Coding: c.100del
MANE Select: NM_205861
dbSNP: rs2075181080
Type: Deletion
Location: chr1:26438203 (GRCh38)
Gene constraint: LOEUF 0.536 · pLI 0.91 (gnomAD)
Structure: AlphaFold pLDDT 95.01 · 9 PDB
Residue 34: a binding site

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.Asp34= Likely benign ★ same residue
DHDDS p.Asp34Glu Likely pathogenic same residue
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.Phe215fs Likely pathogenic ★ same condition
DHDDS p.Thr276fs Likely pathogenic ★ same condition
DHDDS c.323+2_323+5del Conflicting classifications of pathogenicity ★ ⚠ 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-asp34fs (accessed [today's date]).

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