Is DOK5 p.Val261Leu (c.781G>T) pathogenic?

DOK5 p.Val261Leu (c.781G>T) is classified Uncertain significance in DOK5 (ClinVar, Single submitter, 1 submitter; last evaluated 2024-08-04). AlphaMissense: likely benign (0.1044); Absent from gnomAD v4.1.

How common is DOK5 p.Val261Leu (c.781G>T) in the general population?

DOK5 p.Val261Leu (c.781G>T) is absent from gnomAD v4.1 (gnomAD).

What do computational predictors say about DOK5 p.Val261Leu (c.781G>T)?

AlphaMissense predicts likely benign (score 0.1044) — an in-silico prediction, not a clinical call.

DOK5 p.Val261Leu

c.781G>T · VCV3504667

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.1044 · ACMG-weighted

gnomAD v4.1

Absent

absent from gnomAD v4.1

Missense predictors

0/2 damaging

AlphaMissense, SaProt · REVEL no call

Computational evidence

Protein change
AlphaMissense	0.1044	likely benign
REVEL	0.372	indeterminate
SaProt	LLR -6.27	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 12	GERP 1.1, phastCons 1
Regional constraint	o/e 0.95	unconstrained · MANE · 175 kb · p 0.31 · regional, not allelic
Overall
CADD	22.6	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: DOK5
Protein: p.Val261Leu
Coding: c.781G>T
MANE Select: NM_018431
Type: single nucleotide variant
Location: chr20:54643503 (GRCh38)
Gene constraint: LOEUF 0.932 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 78.32 · 1 PDB

Full DOK5 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Similar variants

DOK5 p.Val261Glu Uncertain significance ★ ⚠ same residue
DOK5 p.Ala34Thr Uncertain significance ★★ ⚠ same type
DOK5 p.Ala34Pro Uncertain significance ★ ⚠ same type
DOK5 p.Arg185Gln Uncertain significance ★ ⚠ same type
DOK5 p.Arg186Gln Uncertain significance ★ ⚠ same type
DOK5 p.Arg186Trp Uncertain significance ★ ⚠ same type
DOK5 p.Arg236Leu Uncertain significance ★ ⚠ same type
DOK5 p.Arg253Trp 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/dok5-p-val261leu (accessed [today's date]).

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