Is DHDDS p.Phe215fs (c.644del) pathogenic?

DHDDS p.Phe215fs (c.644del) is classified Likely pathogenic in DHDDS (ClinVar, Single submitter, 1 submitter; last evaluated 2022-09-27). Absent from gnomAD; Associated with retinitis pigmentosa 59.

What condition is associated with DHDDS p.Phe215fs (c.644del)?

DHDDS p.Phe215fs (c.644del) is associated with retinitis pigmentosa 59 (ClinVar).

How common is DHDDS p.Phe215fs (c.644del) in the general population?

DHDDS p.Phe215fs (c.644del) is absent from gnomAD (gnomAD).

DHDDS p.Phe215fs

c.644del · rs2524687283 · VCV1722460

Likely pathogenic Single submitter

Classification

Likely 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 7 of 9
Splicing
SpliceAI	—	not assessed · substitutions only
Constraint at this position
Conservation	phyloP 4	GERP 0.94, 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.Phe215fs
Coding: c.644del
MANE Select: NM_205861
dbSNP: rs2524687283
Type: Deletion
Location: chr1:26457891 (GRCh38)
Gene constraint: LOEUF 0.536 · pLI 0.91 (gnomAD)
Structure: AlphaFold pLDDT 95.01 · 9 PDB
Residue 215: 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 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.Asp34fs Pathogenic ★ same condition
DHDDS p.Thr276fs Likely pathogenic ★ same condition
DHDDS c.323+2_323+5del Conflicting classifications of pathogenicity ★ ⚠ same condition
DHDDS c.766-4del Uncertain significance ★ same condition
DHDDS p.Arg258fs Uncertain significance ★ 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-phe215fs (accessed [today's date]).

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