Is DHDDS p.Arg38Cys (c.112C>T) pathogenic?

DHDDS p.Arg38Cys (c.112C>T) is classified Conflicting classifications of pathogenicity in DHDDS (ClinVar, Conflicting submitters, 4 submitters; last evaluated 2025-02-13). AlphaMissense: likely pathogenic (0.9932); Absent from gnomAD v4.1; Associated with retinitis pigmentosa 59.

What condition is associated with DHDDS p.Arg38Cys (c.112C>T)?

DHDDS p.Arg38Cys (c.112C>T) is associated with retinitis pigmentosa 59, developmental delay and seizures with or without movement abnormalities (ClinVar).

How common is DHDDS p.Arg38Cys (c.112C>T) in the general population?

DHDDS p.Arg38Cys (c.112C>T) is absent from gnomAD v4.1 (gnomAD).

What do computational predictors say about DHDDS p.Arg38Cys (c.112C>T)?

AlphaMissense predicts likely pathogenic (score 0.9932) — an in-silico prediction, not a clinical call.

DHDDS p.Arg38Cys

c.112C>T · rs2124374558 · VCV1467791

Conflicting classifications of pathogenicity Conflicting submitters

Classification

Conflicting classifications of pathogenicity

ClinVar

Review

Conflicting submitters ★☆☆☆

ClinVar · 4 submitters

AlphaMissense

likely pathogenic

0.9932 · ACMG-weighted

gnomAD v4.1

Absent

absent from gnomAD v4.1

Missense predictors

3/3 damaging

AlphaMissense, REVEL, SaProt

Conditions

retinitis pigmentosa 59

Computational evidence

Protein change
AlphaMissense	0.9932	likely pathogenic · top 9% in DHDDS
REVEL	0.918	moderately pathogenic-leaning
SaProt	LLR -16.52	damaging
⇒ AlphaMissense, REVEL and SaProt all call this damaging.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 7.6	GERP 2, phastCons 1
Regional constraint	o/e 0.58	unconstrained · MANE · 9,886 bp · p 3.6e-06 · regional, not allelic
Overall
CADD	34.0	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.Arg38Cys
Coding: c.112C>T
MANE Select: NM_205861
dbSNP: rs2124374558
Type: single nucleotide variant
Location: chr1:26438216 (GRCh38)
Gene constraint: LOEUF 0.536 · pLI 0.91 (gnomAD)
Structure: AlphaFold pLDDT 95.01 · 9 PDB
Residue 38: an α-helix; 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

Also linked: developmental delay and seizures with or without movement abnormalities

Similar variants

DHDDS p.Arg38His Pathogenic/Likely pathogenic ★★ 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
DHDDS p.Arg37Ser Pathogenic ★★ same condition
DHDDS p.Gly35Glu 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-arg38cys (accessed [today's date]).

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