Is DHDDS p.Arg47Gln (c.140G>A) pathogenic?

DHDDS p.Arg47Gln (c.140G>A) is classified Conflicting classifications of pathogenicity in DHDDS (ClinVar, Conflicting submitters, 6 submitters; last evaluated 2026-02-02). AlphaMissense: likely benign (0.2075); Rare (popmax 0.83%, afr); Associated with retinitis pigmentosa.

What condition is associated with DHDDS p.Arg47Gln (c.140G>A)?

DHDDS p.Arg47Gln (c.140G>A) is associated with retinitis pigmentosa, retinitis pigmentosa 59 (ClinVar).

How common is DHDDS p.Arg47Gln (c.140G>A) in the general population?

DHDDS p.Arg47Gln (c.140G>A) is rare (popmax 0.83%, afr) (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.Arg47Gln (c.140G>A)?

AlphaMissense predicts likely benign (score 0.2075) — an in-silico prediction, not a clinical call.

DHDDS p.Arg47Gln

c.140G>A · rs149949619 · VCV283914

Conflicting classifications of pathogenicity Conflicting submitters

Classification

Conflicting classifications of pathogenicity

ClinVar

Review

Conflicting submitters ★☆☆☆

ClinVar · 6 submitters

AlphaMissense

likely benign

0.2075 · ACMG-weighted

gnomAD v4.1

Rare

rare (popmax 0.83%, afr)

Missense predictors

0/3 damaging

AlphaMissense, REVEL, SaProt

Conditions

retinitis pigmentosa

Computational evidence

Protein change
AlphaMissense	0.2075	likely benign
REVEL	0.25	benign-leaning
SaProt	LLR -4.31	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 2.2	GERP 1, phastCons 0.12
Regional constraint	o/e 0.58	unconstrained · MANE · 9,886 bp · p 3.6e-06 · regional, not allelic
Overall
CADD	23.7	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

Grpmax group 0.83% African / African-American · 623/75,054 alleles

Filtering AF 0.776% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.755%

Overall 0.0503% 812/1,614,034 alleles · rare

Ancestry group	Frequency	1 in
African / African-Americangrpmax	0.83%	120
Admixed American	0.142%	706
Remaining individualsnot grpmax-eligible	0.0752%	1,330
European (non-Finnish)	0.00458%	21,851
Ashkenazi Jewishnot grpmax-eligible	0.00338%	29,600
South Asian	0.0022%	45,527

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.Arg47Gln
Coding: c.140G>A
MANE Select: NM_205861
dbSNP: rs149949619
Type: single nucleotide variant
Location: chr1:26438244 (GRCh38)
Gene constraint: LOEUF 0.536 · pLI 0.91 (gnomAD)
Structure: AlphaFold pLDDT 95.01 · 9 PDB
Residue 47: 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

Also linked: retinitis pigmentosa 59

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.Arg47Trp Uncertain significance ★★ ⚠ same residue
DHDDS p.Arg47= Likely benign ★ same residue
DHDDS p.Arg47Leu 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-arg47gln (accessed [today's date]).

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