Is DHDDS p.Asp259Asn (c.775G>A) pathogenic?

DHDDS p.Asp259Asn (c.775G>A) is classified Uncertain significance in DHDDS (ClinVar, Single submitter, 1 submitter; last evaluated 2018-01-13). AlphaMissense: likely benign (0.0869); Absent from gnomAD v4.1; Associated with retinitis pigmentosa.

What condition is associated with DHDDS p.Asp259Asn (c.775G>A)?

DHDDS p.Asp259Asn (c.775G>A) is associated with retinitis pigmentosa (ClinVar).

How common is DHDDS p.Asp259Asn (c.775G>A) in the general population?

DHDDS p.Asp259Asn (c.775G>A) is absent from gnomAD v4.1 (gnomAD).

How is Retinitis pigmentosa inherited?

Typically Autosomal dominant, Autosomal recessive (Orphanet). A genetic counselor can assess individual risk for a family.

What do computational predictors say about DHDDS p.Asp259Asn (c.775G>A)?

AlphaMissense predicts likely benign (score 0.0869) — an in-silico prediction, not a clinical call.

DHDDS p.Asp259Asn

c.775G>A · rs1057515435 · VCV297076

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.0869 · ACMG-weighted

gnomAD v4.1

Absent

absent from gnomAD v4.1

Missense predictors

0/3 damaging

AlphaMissense, REVEL, SaProt

Conditions

retinitis pigmentosa

Computational evidence

Protein change
AlphaMissense	0.0869	likely benign
REVEL	0.152	moderately benign-leaning
SaProt	LLR -6.83	tolerated
⇒ AlphaMissense, REVEL and SaProt all call this tolerated.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 9.9	GERP 1.7, phastCons 1
Regional constraint	o/e 0.89	unconstrained · MANE · 26 kb · p 0.063 · regional, not allelic
Overall
CADD	22.6	PHRED · no single calibrated threshold — expert panels disagree

ClinVar classifies this uncertain; the computational predictors unanimously lean tolerated — a triage signal, not a reclassification

AlphaMissense carries the ACMG weight for missense; REVEL and SaProt are independent agreement signals.

Population frequency

gnomAD v4.1 · exomes + genomes

Absent from gnomAD v4.1. Not observed in any sequenced alleles — a rarity signal (ACMG PM2-supporting), not evidence of pathogenicity on its own.

Variant & gene context

Gene: DHDDS
Protein: p.Asp259Asn
Coding: c.775G>A
MANE Select: NM_205861
dbSNP: rs1057515435
Type: single nucleotide variant
Location: chr1:26468904 (GRCh38)
Gene constraint: LOEUF 0.536 · pLI 0.91 (gnomAD)
Structure: AlphaFold pLDDT 95.01 · 9 PDB
Residue 259: a UniProt-annotated variant site (in rp59; in a patient with congenital disorder of glycosylation); an α-helix

Full DHDDS gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Disease context

retinitis pigmentosa — disease report on Sugi Atlas → Associated genes, phenotypes, clinical trials & treatments

For Retinitis pigmentosa (Orphanet):

Inheritance: Autosomal dominant, Autosomal recessive, Mitochondrial inheritance
Onset: Adolescent, Adult, Childhood
Prevalence: 1-5 / 10 000 (Europe)

Similar variants

DHDDS p.Asp259Gly Uncertain significance ★ ⚠ same residue
DHDDS p.Lys42Glu Pathogenic ★★ ⚠ same condition
DHDDS p.Thr206Ala Likely pathogenic ★★ same condition
DHDDS p.Arg265Gln Uncertain significance ★★ ⚠ same condition
DHDDS p.Arg298Pro Uncertain significance ★★ ⚠ same condition
DHDDS p.Arg306Gln Uncertain significance ★★ ⚠ same condition
DHDDS p.Asn18Ser Uncertain significance ★★ ⚠ same condition
DHDDS p.Gln53Glu 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-asp259asn (accessed [today's date]).

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