Is DHDDS p.Val173Met (c.517G>A) pathogenic?

DHDDS p.Val173Met (c.517G>A) is classified Uncertain significance in DHDDS (ClinVar, Multiple submitters, 2 submitters; last evaluated 2022-10-23). AlphaMissense: likely benign (0.2676); Absent from gnomAD v4.1; Associated with developmental delay and seizures with or without movement abnormalities.

How common is DHDDS p.Val173Met (c.517G>A) in the general population?

DHDDS p.Val173Met (c.517G>A) is absent from gnomAD v4.1 (gnomAD).

What do computational predictors say about DHDDS p.Val173Met (c.517G>A)?

AlphaMissense predicts likely benign (score 0.2676) — an in-silico prediction, not a clinical call.

DHDDS p.Val173Met

Q: What condition is associated with DHDDS p.Val173Met (c.517G>A)?

DHDDS p.Val173Met (c.517G>A) is associated with developmental delay and seizures with or without movement abnormalities, retinitis pigmentosa 59 (ClinVar).

c.517G>A · rs2075282159 · VCV1333626

Uncertain significance Multiple submitters

Classification

Uncertain significance

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 2 submitters

AlphaMissense

likely benign

0.2676 · ACMG-weighted

gnomAD v4.1

Absent

absent from gnomAD v4.1

Missense predictors

2/3 damaging

AlphaMissense, REVEL, SaProt

Conditions

developmental delay and seizures with or without movement abnormalities

Computational evidence

Protein change
AlphaMissense	0.2676	likely benign
REVEL	0.763	pathogenic-leaning
SaProt	LLR -11.65	damaging
⇒ REVEL and SaProt call this damaging; AlphaMissense does not.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 12	GERP 1.9, phastCons 1
Regional constraint	o/e 0.89	unconstrained · MANE · 26 kb · p 0.063 · regional, not allelic
Overall
CADD	29.4	PHRED · no single calibrated threshold — expert panels disagree

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.Val173Met
Coding: c.517G>A
MANE Select: NM_205861
dbSNP: rs2075282159
Type: single nucleotide variant
Location: chr1:26447635 (GRCh38)
Gene constraint: LOEUF 0.536 · pLI 0.91 (gnomAD)
Structure: AlphaFold pLDDT 95.01 · 9 PDB
Residue 173: 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

developmental delay and seizures with or without movement abnormalities — disease report on Sugi Atlas → Associated genes, phenotypes, clinical trials & treatments

Also linked: retinitis pigmentosa 59

Similar variants

DHDDS p.Val173= Likely benign ★★ same residue
DHDDS p.Val173fs Pathogenic/Likely pathogenic ★★ same residue
DHDDS p.Val173Ala Uncertain significance ★ ⚠ same residue
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

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-val173met (accessed [today's date]).

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