Is DHDDS p.Phe15Tyr (c.44T>A) pathogenic?

DHDDS p.Phe15Tyr (c.44T>A) is classified Uncertain significance in DHDDS (ClinVar, Single submitter, 1 submitter; last evaluated 2024-02-16). AlphaMissense: likely benign (0.2798); Absent from gnomAD v4.1; Associated with retinitis pigmentosa 59.

What condition is associated with DHDDS p.Phe15Tyr (c.44T>A)?

DHDDS p.Phe15Tyr (c.44T>A) is associated with retinitis pigmentosa 59 (ClinVar).

How common is DHDDS p.Phe15Tyr (c.44T>A) in the general population?

DHDDS p.Phe15Tyr (c.44T>A) is absent from gnomAD v4.1 (gnomAD).

What do computational predictors say about DHDDS p.Phe15Tyr (c.44T>A)?

AlphaMissense predicts likely benign (score 0.2798) — an in-silico prediction, not a clinical call.

DHDDS p.Phe15Tyr

c.44T>A · rs2524405397 · VCV2762104

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.2798 · ACMG-weighted

gnomAD v4.1

Absent

absent from gnomAD v4.1

Missense predictors

1/3 damaging

AlphaMissense, REVEL, SaProt

Conditions

retinitis pigmentosa 59

Computational evidence

Protein change
AlphaMissense	0.2798	likely benign
REVEL	0.136	moderately benign-leaning
SaProt	LLR -10.56	damaging
⇒ SaProt calls this damaging; AlphaMissense and REVEL do not.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 7.9	GERP 2, phastCons 1
Regional constraint	o/e 0.58	unconstrained · MANE · 9,886 bp · p 3.6e-06 · regional, not allelic
Overall
CADD	25.5	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.Phe15Tyr
Coding: c.44T>A
MANE Select: NM_205861
dbSNP: rs2524405397
Type: single nucleotide variant
Location: chr1:26432989 (GRCh38)
Gene constraint: LOEUF 0.536 · pLI 0.91 (gnomAD)
Structure: AlphaFold pLDDT 95.01 · 9 PDB
Residue 15: an α-helix

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

Similar variants

DHDDS p.Phe15= 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
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-phe15tyr (accessed [today's date]).

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