Is DOK3 p.Arg90Leu (c.269G>T) pathogenic?

DOK3 p.Arg90Leu (c.269G>T) is classified Uncertain significance in DOK3 (ClinVar, Single submitter, 1 submitter; last evaluated 2023-08-02). AlphaMissense: ambiguous (0.4427); Absent from gnomAD v4.1.

How common is DOK3 p.Arg90Leu (c.269G>T) in the general population?

DOK3 p.Arg90Leu (c.269G>T) is absent from gnomAD v4.1 (gnomAD).

What do computational predictors say about DOK3 p.Arg90Leu (c.269G>T)?

AlphaMissense predicts ambiguous (score 0.4427) — an in-silico prediction, not a clinical call.

DOK3 p.Arg90Leu

c.269G>T · rs142573859 · VCV2615358

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

ambiguous

0.4427 · ACMG-weighted

gnomAD v4.1

Not reported

no allele count reported in gnomAD v4.1 (AN 1,598,104)

Missense predictors

1/2 damaging

REVEL, SaProt · AlphaMissense no call

Computational evidence

Protein change
AlphaMissense	0.4427	ambiguous
REVEL	0.1	moderately benign-leaning
SaProt	LLR -10.19	damaging
⇒ SaProt calls this damaging; REVEL does not; AlphaMissense makes no call.
Splicing
SpliceAI	<0.2	all four deltas below 0.2 · C>T here scores Δ0.22 · evaluated, not missing
Constraint at this position
Conservation	phyloP 2.7	GERP -0.5, phastCons 1
Regional constraint	o/e 1.01	unconstrained · MANE · 5,554 bp · p 0.73 · regional, not allelic
Overall
CADD	23.4	PHRED · no single calibrated threshold — expert panels disagree

AlphaMissense carries the ACMG weight for missense; REVEL and SaProt are independent agreement signals.

⚠ Isoform check: AlphaMissense numbered on a different transcript (AM R146L vs ClinVar R90L) — verify the residue.

Population frequency

gnomAD v4.1 · exomes + genomes

No allele count reported in gnomAD v4.1 (AN 1,598,104). This is missing data, not an absence: the variant may or may not be present in gnomAD. Rarity (ACMG PM2) and BA1/BS1 cannot be assessed for it.

Variant & gene context

Gene: DOK3
Protein: p.Arg90Leu
Coding: c.269G>T
MANE Select: NM_001308236
dbSNP: rs142573859
Type: single nucleotide variant
Location: chr5:177508340 (GRCh38)
Gene constraint: LOEUF 1.47 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 65.94
Residue 90: the ph domain

Full DOK3 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Similar variants

DOK3 p.Arg90Gln Uncertain significance ★ ⚠ same residue
DOK3 c.-102G>T Uncertain significance ★ ⚠ same type
DOK3 c.-181C>T Uncertain significance ★ ⚠ same type
DOK3 c.-182G>A Uncertain significance ★ ⚠ same type
DOK3 c.-182G>C Uncertain significance ★ ⚠ same type
DOK3 c.-23C>T Uncertain significance ★ ⚠ same type
DOK3 c.-35G>A Uncertain significance ★ ⚠ same type
DOK3 c.-62C>T Uncertain significance ★ ⚠ same type

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/dok3-p-arg90leu (accessed [today's date]).

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