Is DOCK11 p.Gln258Arg (c.773A>G) pathogenic?

DOCK11 p.Gln258Arg (c.773A>G) is classified Uncertain significance in DOCK11 (ClinVar, Single submitter, 1 submitter; last evaluated 2025-04-11). AlphaMissense: likely benign (0.1389); Ultra-rare (popmax 0.0594%, afr).

How common is DOCK11 p.Gln258Arg (c.773A>G) in the general population?

DOCK11 p.Gln258Arg (c.773A>G) is ultra-rare (popmax 0.0594%, afr) (gnomAD).

What do computational predictors say about DOCK11 p.Gln258Arg (c.773A>G)?

AlphaMissense predicts likely benign (score 0.1389) — an in-silico prediction, not a clinical call.

DOCK11 p.Gln258Arg

c.773A>G · VCV4014081

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.1389 · ACMG-weighted

gnomAD v4.1

Rare

ultra-rare (popmax 0.0594%, afr)

Missense predictors

0/2 damaging

AlphaMissense, SaProt · REVEL no call

Computational evidence

Protein change
AlphaMissense	0.1389	likely benign
REVEL	0.291	indeterminate
SaProt	LLR -6.66	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 8	GERP 1.2, phastCons 1
Regional constraint	o/e 0.76	unconstrained · MANE · 190 kb · p 2e-21 · regional, not allelic
Overall
CADD	21.7	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 0.0594% African / African-American · 34/57,253 alleles

Filtering AF 0.0437% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.0382%

Overall 0.00364% 44/1,207,158 alleles · ultra-rare

Ancestry group	Frequency	1 in
African / African-Americangrpmax	0.0594%	1,684
Admixed American	0.0109%	9,139
Remaining individualsnot grpmax-eligible	0.00421%	23,751
European (non-Finnish)	0.000336%	297,515

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: DOCK11
Protein: p.Gln258Arg
Coding: c.773A>G
MANE Select: NM_144658
Type: single nucleotide variant
Location: chrX:118566084 (GRCh38)
Structure: AlphaFold pLDDT 79.65
Residue 258: the ph domain

Full DOCK11 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Similar variants

DOCK11 p.Ala1222Val Uncertain significance ★★ ⚠ same type
DOCK11 p.Ala1665Val Uncertain significance ★★ ⚠ same type
DOCK11 p.Leu781His Uncertain significance ★★ ⚠ same type
DOCK11 p.Gln866Arg Benign ★★ same type
DOCK11 p.Ser842Leu Likely benign ★★ same type
DOCK11 c.1718+5G>A Pathogenic ★ same type
DOCK11 c.392+1G>A Likely pathogenic ★ same type
DOCK11 c.4582-1G>A Likely pathogenic ★ 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/dock11-p-gln258arg (accessed [today's date]).

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