Is DHDDS p.Arg306Gln (c.917G>A) pathogenic?

DHDDS p.Arg306Gln (c.917G>A) is classified Uncertain significance in DHDDS (ClinVar, Multiple submitters, 2 submitters; last evaluated 2022-09-06). AlphaMissense: ambiguous (0.4183); Ultra-rare (popmax 0.067%, sas); Associated with retinitis pigmentosa.

What condition is associated with DHDDS p.Arg306Gln (c.917G>A)?

DHDDS p.Arg306Gln (c.917G>A) is associated with retinitis pigmentosa, retinitis pigmentosa 59 (ClinVar).

How common is DHDDS p.Arg306Gln (c.917G>A) in the general population?

DHDDS p.Arg306Gln (c.917G>A) is ultra-rare (popmax 0.067%, sas) (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.Arg306Gln (c.917G>A)?

AlphaMissense predicts ambiguous (score 0.4183) — an in-silico prediction, not a clinical call.

DHDDS p.Arg306Gln

c.917G>A · rs543487813 · VCV297078

Uncertain significance Multiple submitters

Classification

Uncertain significance

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 2 submitters

AlphaMissense

ambiguous

0.4183 · ACMG-weighted

gnomAD v4.1

Rare

ultra-rare (popmax 0.067%, sas)

Missense predictors

0/2 damaging

REVEL, SaProt · AlphaMissense no call

Conditions

retinitis pigmentosa

Computational evidence

Protein change
AlphaMissense	0.4183	ambiguous
REVEL	0.203	benign-leaning
SaProt	LLR -7.51	tolerated
⇒ REVEL and SaProt both call this tolerated; AlphaMissense makes no call.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 12	GERP 1.7, phastCons 1
Regional constraint	o/e 0.89	unconstrained · MANE · 26 kb · p 0.063 · regional, not allelic
Overall
CADD	33.0	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

Grpmax group 0.067% South Asian · 61/91,068 alleles

Filtering AF 0.0535% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.0486%

Overall 0.00514% 83/1,613,928 alleles · ultra-rare

Ancestry group	Frequency	1 in
South Asiangrpmax	0.067%	1,493
Admixed American	0.005%	20,010
Remaining individualsnot grpmax-eligible	0.0048%	20,826
African / African-American	0.00133%	75,064
European (non-Finnish)	0.00127%	78,669

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.Arg306Gln
Coding: c.917G>A
MANE Select: NM_205861
dbSNP: rs543487813
Type: single nucleotide variant
Location: chr1:26469046 (GRCh38)
Gene constraint: LOEUF 0.536 · pLI 0.91 (gnomAD)
Structure: AlphaFold pLDDT 95.01 · 9 PDB
Residue 306: 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

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.Arg306Trp Uncertain significance ★★ ⚠ same residue
DHDDS p.Arg306= Likely benign ★ 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

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-arg306gln (accessed [today's date]).

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