Is DOCK3 p.Val290Ile (c.868G>A) pathogenic?

DOCK3 p.Val290Ile (c.868G>A) is classified Uncertain significance in DOCK3 (ClinVar, Single submitter, 1 submitter; last evaluated 2023-05-24). AlphaMissense: likely benign (0.0859); Very rare (popmax 0.00989%, sas); Associated with Inborn genetic diseases.

What condition is associated with DOCK3 p.Val290Ile (c.868G>A)?

DOCK3 p.Val290Ile (c.868G>A) is associated with Inborn genetic diseases (ClinVar).

How common is DOCK3 p.Val290Ile (c.868G>A) in the general population?

DOCK3 p.Val290Ile (c.868G>A) is very rare (popmax 0.00989%, sas) (gnomAD).

What do computational predictors say about DOCK3 p.Val290Ile (c.868G>A)?

AlphaMissense predicts likely benign (score 0.0859) — an in-silico prediction, not a clinical call.

DOCK3 p.Val290Ile

c.868G>A · rs758629699 · VCV2510122

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.0859 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 0.00989%, sas)

Missense predictors

0/3 damaging

AlphaMissense, REVEL, SaProt

Conditions

Inborn genetic diseases

Computational evidence

Protein change
AlphaMissense	0.0859	likely benign
REVEL	0.084	moderately benign-leaning
SaProt	LLR -7.83	tolerated
⇒ AlphaMissense, REVEL and SaProt all call this tolerated.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 8.5	GERP 1.4, phastCons 1
Regional constraint	o/e 0.85	unconstrained · MANE · 550 kb · p 0.00035 · regional, not allelic
Overall
CADD	22.4	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

Grpmax group 0.00989% South Asian · 9/90,966 alleles

Filtering AF 0.00514% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.00376%

Overall 0.00304% 49/1,612,976 alleles · very rare

Ancestry group	Frequency	1 in
South Asiangrpmax	0.00989%	10,107
Admixed American	0.005%	19,995
East Asian	0.00446%	22,436
European (non-Finnish)	0.00271%	36,856
African / African-American	0.00267%	37,427
Remaining individualsnot grpmax-eligible	0.0016%	62,430

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: DOCK3
Protein: p.Val290Ile
Coding: c.868G>A
MANE Select: NM_004947
dbSNP: rs758629699
Type: single nucleotide variant
Location: chr3:51159283 (GRCh38)
Gene constraint: LOEUF 0.298 · pLI 1.00 (gnomAD)
Structure: AlphaFold pLDDT 75.52
Residue 290: a UniProt-annotated variant site (in nedidha)

Full DOCK3 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Disease context

Inborn genetic diseases — disease report on Sugi Atlas → Associated genes, phenotypes, clinical trials & treatments

Similar variants

DOCK3 p.Arg1609Trp Uncertain significance ★★ ⚠ same condition
DOCK3 p.Arg1787Gln Uncertain significance ★★ ⚠ same condition
DOCK3 p.Arg2020Cys Uncertain significance ★★ ⚠ same condition
DOCK3 p.Arg392Gln Uncertain significance ★★ ⚠ same condition
DOCK3 p.Arg486His Uncertain significance ★★ ⚠ same condition
DOCK3 p.Gly1699Cys Uncertain significance ★★ ⚠ same condition
DOCK3 p.Leu1982Arg Uncertain significance ★★ ⚠ same condition
DOCK3 p.Lys343Arg 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/dock3-p-val290ile (accessed [today's date]).

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