Is DOCK4 p.Thr982Ala (c.2944A>G) pathogenic?

DOCK4 p.Thr982Ala (c.2944A>G) is classified Uncertain significance in DOCK4 (ClinVar, Single submitter, 1 submitter; last evaluated 2025-09-05). AlphaMissense: likely benign (0.2997); Ultra-rare (popmax 0.017%, mid).

How common is DOCK4 p.Thr982Ala (c.2944A>G) in the general population?

DOCK4 p.Thr982Ala (c.2944A>G) is ultra-rare (popmax 0.017%, mid) (gnomAD).

What do computational predictors say about DOCK4 p.Thr982Ala (c.2944A>G)?

AlphaMissense predicts likely benign (score 0.2997) — an in-silico prediction, not a clinical call.

DOCK4 p.Thr982Ala

c.2944A>G · VCV4243923

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.2997 · ACMG-weighted

gnomAD v4.1

Rare

ultra-rare (popmax 0.017%, mid)

Missense predictors

0/3 damaging

AlphaMissense, REVEL, SaProt

Computational evidence

Protein change
AlphaMissense	0.2997	likely benign
REVEL	0.126	moderately benign-leaning
SaProt	LLR -7.16	tolerated
⇒ AlphaMissense, REVEL and SaProt all call this tolerated.
Splicing
SpliceAI	—	not looked up on this page · why
Constraint at this position
Conservation	phyloP 7.9	GERP 2.8, phastCons 1
Regional constraint	o/e 0.80	unconstrained · MANE · 465 kb · p 2.8e-18 · regional, not allelic
Overall
CADD	25.7	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 0.017% Middle Eastern · 1/5,868 alleles

Filtering AF 0.00137% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.00114%

Overall 0.00185% 28/1,511,434 alleles · ultra-rare

Ancestry group	Frequency	1 in
Middle Easterngrpmax	0.017%	5,868
South Asian	0.0037%	27,057
European (non-Finnish)	0.00206%	48,590
Remaining individualsnot grpmax-eligible	0.00171%	58,590

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: DOCK4
Protein: p.Thr982Ala
Coding: c.2944A>G
Type: single nucleotide variant
Location: chr7:111811936 (GRCh38)

Full DOCK4 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

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/dock4-p-thr982ala (accessed [today's date]).

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