Is DHDDS p.Lys57Arg (c.170A>G) pathogenic?

DHDDS p.Lys57Arg (c.170A>G) is classified Uncertain significance in DHDDS (ClinVar, Single submitter, 1 submitter; last evaluated 2023-10-01). AlphaMissense: likely benign (0.1585); Absent from gnomAD v4.1; Associated with inherited retinal dystrophy.

What condition is associated with DHDDS p.Lys57Arg (c.170A>G)?

DHDDS p.Lys57Arg (c.170A>G) is associated with inherited retinal dystrophy (ClinVar).

How common is DHDDS p.Lys57Arg (c.170A>G) in the general population?

DHDDS p.Lys57Arg (c.170A>G) is absent from gnomAD v4.1 (gnomAD).

What do computational predictors say about DHDDS p.Lys57Arg (c.170A>G)?

AlphaMissense predicts likely benign (score 0.1585) — an in-silico prediction, not a clinical call.

DHDDS p.Lys57Arg

c.170A>G · rs2524466453 · VCV3028656

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.1585 · ACMG-weighted

gnomAD v4.1

Absent

absent from gnomAD v4.1

Missense predictors

0/2 damaging

AlphaMissense, SaProt · REVEL no call

Conditions

inherited retinal dystrophy

Computational evidence

Protein change
AlphaMissense	0.1585	likely benign
REVEL	0.342	indeterminate
SaProt	LLR -9.24	tolerated
⇒ AlphaMissense and SaProt both call this tolerated; REVEL makes no call.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 9.2	GERP 2, phastCons 1
Regional constraint	o/e 0.58	unconstrained · MANE · 9,886 bp · p 3.6e-06 · regional, not allelic
Overall
CADD	27.4	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

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.Lys57Arg
Coding: c.170A>G
MANE Select: NM_205861
dbSNP: rs2524466453
Type: single nucleotide variant
Location: chr1:26438274 (GRCh38)
Gene constraint: LOEUF 0.536 · pLI 0.91 (gnomAD)
Structure: AlphaFold pLDDT 95.01 · 9 PDB
Residue 57: an α-helix

Full DHDDS gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Disease context

inherited retinal dystrophy — disease report on Sugi Atlas → Associated genes, phenotypes, clinical trials & treatments

Similar variants

DHDDS p.Lys57= Likely benign ★ same residue
DHDDS p.Ala77Thr Uncertain significance ★★ ⚠ same condition
DHDDS p.Arg327Cys Uncertain significance ★★ ⚠ same condition
DHDDS p.Asp123Asn Uncertain significance ★★ ⚠ same condition
DHDDS p.Asp323Glu Uncertain significance ★★ ⚠ same condition
DHDDS p.Leu254Pro Uncertain significance ★★ ⚠ same condition
DHDDS p.Leu286Ile Uncertain significance ★★ ⚠ same condition
DHDDS p.Lys84Arg Uncertain significance ★★ ⚠ 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-lys57arg (accessed [today's date]).

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