Is DHDDS p.Ala165Val (c.494C>T) pathogenic?

DHDDS p.Ala165Val (c.494C>T) is classified Uncertain significance in DHDDS (ClinVar, Single submitter, 1 submitter; last evaluated 2023-10-01). AlphaMissense: likely pathogenic (0.8088); Very rare (popmax 0.00891%, eas); Associated with inherited retinal dystrophy.

What condition is associated with DHDDS p.Ala165Val (c.494C>T)?

DHDDS p.Ala165Val (c.494C>T) is associated with inherited retinal dystrophy (ClinVar).

How common is DHDDS p.Ala165Val (c.494C>T) in the general population?

DHDDS p.Ala165Val (c.494C>T) is very rare (popmax 0.00891%, eas) (gnomAD).

What do computational predictors say about DHDDS p.Ala165Val (c.494C>T)?

AlphaMissense predicts likely pathogenic (score 0.8088) — an in-silico prediction, not a clinical call.

DHDDS p.Ala165Val

c.494C>T · rs1383907275 · VCV3028668

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely pathogenic

0.8088 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 0.00891%, eas)

Missense predictors

2/2 damaging

AlphaMissense, SaProt · REVEL no call

Conditions

inherited retinal dystrophy

Computational evidence

Protein change
AlphaMissense	0.8088	likely pathogenic
REVEL	0.62	indeterminate
SaProt	LLR -12.55	damaging
⇒ AlphaMissense and SaProt both call this damaging; REVEL makes no call.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 7.6	GERP 1.9, phastCons 1
Regional constraint	o/e 0.89	unconstrained · MANE · 26 kb · p 0.063 · regional, not allelic
Overall
CADD	29.4	PHRED · no single calibrated threshold — expert panels disagree

ClinVar classifies this uncertain; the computational predictors unanimously lean damaging — 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 0.00891% East Asian · 4/44,876 alleles

Filtering AF 0.00298% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.0018%

Overall 0.000342% 5/1,461,882 alleles · very rare

Ancestry group	Frequency	1 in
East Asiangrpmax	0.00891%	11,219
Admixed American	0.00167%	60,014

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.Ala165Val
Coding: c.494C>T
MANE Select: NM_205861
dbSNP: rs1383907275
Type: single nucleotide variant
Location: chr1:26447612 (GRCh38)
Gene constraint: LOEUF 0.536 · pLI 0.91 (gnomAD)
Structure: AlphaFold pLDDT 95.01 · 9 PDB
Residue 165: 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

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

Similar variants

DHDDS p.Ala165Ser Uncertain significance ★ 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-ala165val (accessed [today's date]).

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