Is DHTKD1 p.Ile762Val (c.2284A>G) pathogenic?

DHTKD1 p.Ile762Val (c.2284A>G) is classified Uncertain significance in DHTKD1 (ClinVar, Single submitter, 1 submitter; last evaluated 2021-08-18). AlphaMissense: likely benign (0.0784); Absent from gnomAD v4.1; Associated with 2-aminoadipic 2-oxoadipic aciduria.

What condition is associated with DHTKD1 p.Ile762Val (c.2284A>G)?

DHTKD1 p.Ile762Val (c.2284A>G) is associated with 2-aminoadipic 2-oxoadipic aciduria (ClinVar).

How common is DHTKD1 p.Ile762Val (c.2284A>G) in the general population?

DHTKD1 p.Ile762Val (c.2284A>G) is absent from gnomAD v4.1 (gnomAD).

How is 2-aminoadipic 2-oxoadipic aciduria inherited?

Typically Autosomal recessive (Orphanet). A genetic counselor can assess individual risk for a family.

What do computational predictors say about DHTKD1 p.Ile762Val (c.2284A>G)?

AlphaMissense predicts likely benign (score 0.0784) — an in-silico prediction, not a clinical call.

DHTKD1 p.Ile762Val

c.2284A>G · rs2131624242 · VCV1375890

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.0784 · ACMG-weighted

gnomAD v4.1

Absent

absent from gnomAD v4.1

Missense predictors

0/2 damaging

AlphaMissense, SaProt · REVEL no call

Conditions

2-aminoadipic 2-oxoadipic aciduria

Computational evidence

Protein change
AlphaMissense	0.0784	likely benign
REVEL	0.602	indeterminate
SaProt	LLR -7.96	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 5.3	GERP 1.6, phastCons 1
Regional constraint	o/e 1.05	unconstrained · MANE · 52 kb · p 0.072 · regional, not allelic
Overall
CADD	19.54	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: DHTKD1
Protein: p.Ile762Val
Coding: c.2284A>G
MANE Select: NM_018706
dbSNP: rs2131624242
Type: single nucleotide variant
Location: chr10:12113029 (GRCh38)
Gene constraint: LOEUF 0.864 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 95.19 · 8 PDB
Residue 762: a UniProt-annotated variant site (in aakad); a β-strand

Full DHTKD1 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Disease context

2-aminoadipic 2-oxoadipic aciduria — disease report on Sugi Atlas → Associated genes, phenotypes, clinical trials & treatments

For 2-aminoadipic 2-oxoadipic aciduria (Orphanet):

Inheritance: Autosomal recessive
Onset: Childhood, Infancy

Similar variants

DHTKD1 p.Ile762Thr Uncertain significance ★ ⚠ same residue
DHTKD1 p.Ile762del Uncertain significance ★ same residue
DHTKD1 c.1671+1G>A Likely pathogenic ★★ same condition
DHTKD1 c.1897-1G>A Pathogenic/Likely pathogenic ★★ same condition
DHTKD1 c.2320-2A>T Likely pathogenic ★★ same condition
DHTKD1 c.2572+1G>A Likely pathogenic ★★ same condition
DHTKD1 p.Arg163Ter Pathogenic ★★ same condition
DHTKD1 p.Arg410Ter 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/dhtkd1-p-ile762val (accessed [today's date]).

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