Is DHDDS p.Gln53Glu (c.157C>G) pathogenic?

DHDDS p.Gln53Glu (c.157C>G) is classified Uncertain significance in DHDDS (ClinVar, Multiple submitters, 3 submitters; last evaluated 2026-01-27). AlphaMissense: likely benign (0.0955); Very rare (popmax 0.000424%, nfe); Associated with retinitis pigmentosa.

What condition is associated with DHDDS p.Gln53Glu (c.157C>G)?

DHDDS p.Gln53Glu (c.157C>G) is associated with retinitis pigmentosa, retinitis pigmentosa 59 (ClinVar).

How common is DHDDS p.Gln53Glu (c.157C>G) in the general population?

DHDDS p.Gln53Glu (c.157C>G) is very rare (popmax 0.000424%, nfe) (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.Gln53Glu (c.157C>G)?

AlphaMissense predicts likely benign (score 0.0955) — an in-silico prediction, not a clinical call.

DHDDS p.Gln53Glu

c.157C>G · rs1057515434 · VCV297072

Uncertain significance Multiple submitters

Classification

Uncertain significance

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 3 submitters

AlphaMissense

likely benign

0.0955 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 0.000424%, nfe)

Missense predictors

0/3 damaging

AlphaMissense, REVEL, SaProt

Conditions

retinitis pigmentosa

Computational evidence

Protein change
AlphaMissense	0.0955	likely benign
REVEL	0.223	benign-leaning
SaProt	LLR -8.91	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 2.6	GERP 1.1, phastCons 0.99
Regional constraint	o/e 0.58	unconstrained · MANE · 9,886 bp · p 3.6e-06 · regional, not allelic
Overall
CADD	22.1	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

Grpmax group 0.000424% European (non-Finnish) · 5/1,179,936 alleles

Filtering AF 0.000124% ClinGen BA1/BS1 input FAF95, joint · FAF99 9e-05%

Overall 0.000342% 5/1,461,676 alleles · very rare

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.Gln53Glu
Coding: c.157C>G
MANE Select: NM_205861
dbSNP: rs1057515434
Type: single nucleotide variant
Location: chr1:26438261 (GRCh38)
Gene constraint: LOEUF 0.536 · pLI 0.91 (gnomAD)
Structure: AlphaFold pLDDT 95.01 · 9 PDB
Residue 53: 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 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
DHDDS p.Lys42Glu 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-gln53glu (accessed [today's date]).

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