Is DOCK3 p.Val1962Ile (c.5884G>A) pathogenic?

DOCK3 p.Val1962Ile (c.5884G>A) is classified Uncertain significance in DOCK3 (ClinVar, Single submitter, 1 submitter; last evaluated 2021-05-13). AlphaMissense: likely benign (0.088); Ultra-rare (popmax 0.0154%, sas); Associated with Inborn genetic diseases.

What condition is associated with DOCK3 p.Val1962Ile (c.5884G>A)?

DOCK3 p.Val1962Ile (c.5884G>A) is associated with Inborn genetic diseases (ClinVar).

How common is DOCK3 p.Val1962Ile (c.5884G>A) in the general population?

DOCK3 p.Val1962Ile (c.5884G>A) is ultra-rare (popmax 0.0154%, sas) (gnomAD).

What do computational predictors say about DOCK3 p.Val1962Ile (c.5884G>A)?

AlphaMissense predicts likely benign (score 0.088) — an in-silico prediction, not a clinical call.

DOCK3 p.Val1962Ile

c.5884G>A · rs781988049 · VCV2383644

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.088 · ACMG-weighted

gnomAD v4.1

Rare

ultra-rare (popmax 0.0154%, sas)

Missense predictors

0/3 damaging

AlphaMissense, REVEL, SaProt

Conditions

Inborn genetic diseases

Computational evidence

Protein change
AlphaMissense	0.088	likely benign
REVEL	0.192	benign-leaning
SaProt	LLR -6.69	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 9.7	GERP 2.2, phastCons 1
Regional constraint	o/e 1.03	unconstrained · MANE · 310 bp · p 0.72 · regional, not allelic
Overall
CADD	23.9	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 0.0154% South Asian · 14/91,078 alleles

Filtering AF 0.0092% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.00735%

Overall 0.00477% 77/1,613,030 alleles · ultra-rare

Ancestry group	Frequency	1 in
South Asiangrpmax	0.0154%	6,506
Admixed American	0.0133%	7,499
Remaining individualsnot grpmax-eligible	0.00961%	10,409
European (non-Finnish)	0.0039%	25,649
East Asian	0.00223%	44,888
Finnishnot grpmax-eligible	0.00158%	63,272
African / African-American	0.00134%	74,898

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.Val1962Ile
Coding: c.5884G>A
MANE Select: NM_004947
dbSNP: rs781988049
Type: single nucleotide variant
Location: chr3:51381350 (GRCh38)
Gene constraint: LOEUF 0.298 · pLI 1.00 (gnomAD)
Structure: AlphaFold pLDDT 75.52
Residue 1962: a UniProt-annotated variant site (in nedidha); the 'disordered' region

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-val1962ile (accessed [today's date]).

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