Is DOCK3 p.Arg776Gln (c.2327G>A) pathogenic?

DOCK3 p.Arg776Gln (c.2327G>A) is classified Uncertain significance in DOCK3 (ClinVar, Single submitter, 1 submitter; last evaluated 2026-02-01). AlphaMissense: likely benign (0.1192); Ultra-rare (popmax 0.0165%, mid).

How common is DOCK3 p.Arg776Gln (c.2327G>A) in the general population?

DOCK3 p.Arg776Gln (c.2327G>A) is ultra-rare (popmax 0.0165%, mid) (gnomAD).

What do computational predictors say about DOCK3 p.Arg776Gln (c.2327G>A)?

AlphaMissense predicts likely benign (score 0.1192) — an in-silico prediction, not a clinical call.

DOCK3 p.Arg776Gln

c.2327G>A · VCV4823454

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.1192 · ACMG-weighted

gnomAD v4.1

Rare

ultra-rare (popmax 0.0165%, mid)

Missense predictors

0/2 damaging

AlphaMissense, SaProt · REVEL no call

Computational evidence

Protein change
AlphaMissense	0.1192	likely benign
REVEL	0.319	indeterminate
SaProt	LLR -6.50	tolerated
⇒ AlphaMissense and SaProt both call this tolerated; REVEL makes no call.
Splicing
SpliceAI	Δ0.21	donor loss · deltas
Constraint at this position
Conservation	phyloP 12	GERP 2.9, phastCons 1
Regional constraint	o/e 0.73	unconstrained · MANE · 154 kb · p 4e-32 · regional, not allelic
Overall
CADD	28.3	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 0.0165% Middle Eastern · 1/6,078 alleles

Filtering AF 0.00106% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.000495%

Overall 0.00093% 15/1,613,628 alleles · ultra-rare

Ancestry group	Frequency	1 in
Middle Easterngrpmax	0.0165%	6,078
African / African-American	0.00401%	24,960
Admixed American	0.00333%	29,986
East Asian	0.00223%	44,886
European (non-Finnish)	0.000678%	147,477

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.Arg776Gln
Coding: c.2327G>A
MANE Select: NM_004947
Type: single nucleotide variant
Location: chr3:51260298 (GRCh38)
Gene constraint: LOEUF 0.298 · pLI 1.00 (gnomAD)
Structure: AlphaFold pLDDT 75.52
Residue 776: a UniProt-annotated variant site (in nedidha)

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

Similar variants

DOCK3 p.Arg1609Trp Uncertain significance ★★ ⚠ same type
DOCK3 p.Arg1787Gln Uncertain significance ★★ ⚠ same type
DOCK3 p.Arg2020Cys Uncertain significance ★★ ⚠ same type
DOCK3 p.Arg392Gln Uncertain significance ★★ ⚠ same type
DOCK3 p.Arg486His Uncertain significance ★★ ⚠ same type
DOCK3 p.Gly1699Cys Uncertain significance ★★ ⚠ same type
DOCK3 p.Leu1982Arg Uncertain significance ★★ ⚠ same type
DOCK3 p.Lys1296Arg 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/dock3-p-arg776gln (accessed [today's date]).

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