Is DOCK6 p.Arg249His (c.746G>A) pathogenic?

DOCK6 p.Arg249His (c.746G>A) is classified Likely benign in DOCK6 (ClinVar, Single submitter, 1 submitter; last evaluated 2023-12-16). AlphaMissense: likely benign (0.0764); Very rare (popmax 0.00512%, nfe); Associated with Inborn genetic diseases.

What condition is associated with DOCK6 p.Arg249His (c.746G>A)?

DOCK6 p.Arg249His (c.746G>A) is associated with Inborn genetic diseases (ClinVar).

How common is DOCK6 p.Arg249His (c.746G>A) in the general population?

DOCK6 p.Arg249His (c.746G>A) is very rare (popmax 0.00512%, nfe) (gnomAD).

What do computational predictors say about DOCK6 p.Arg249His (c.746G>A)?

AlphaMissense predicts likely benign (score 0.0764) — an in-silico prediction, not a clinical call.

DOCK6 p.Arg249His

c.746G>A · rs372648250 · VCV3085087

Likely benign Single submitter

Classification

Likely benign

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.0764 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 0.00512%, nfe)

Missense predictors

0/3 damaging

AlphaMissense, REVEL, SaProt

Conditions

Inborn genetic diseases

Computational evidence

Protein change
AlphaMissense	0.0764	likely benign
REVEL	0.067	moderately benign-leaning
SaProt	LLR -5.36	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 -0.51	GERP -4.8, phastCons 0.008
Regional constraint	o/e 0.92	unconstrained · MANE · 63 kb · p 1.8e-05 · regional, not allelic
Overall
CADD	7.705	PHRED · no single calibrated threshold — expert panels disagree

AlphaMissense carries the ACMG weight for missense; REVEL and SaProt are independent agreement signals.

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.00512% European (non-Finnish) · 59/1,153,064 alleles

Filtering AF 0.00403% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.00369%

Overall 0.00421% 66/1,566,698 alleles · very rare

Ancestry group	Frequency	1 in
European (non-Finnish)grpmax	0.00512%	19,543
South Asian	0.00446%	22,441
Remaining individualsnot grpmax-eligible	0.00336%	29,795
African / African-American	0.00138%	72,302

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: DOCK6
Protein: p.Arg249His
Coding: c.746G>A
MANE Select: NM_020812
dbSNP: rs372648250
Type: single nucleotide variant
Location: chr19:11248126 (GRCh38)
Gene constraint: LOEUF 0.87 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 77.78 · 7 PDB
Residue 249: the 'disordered' region

Full DOCK6 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

DOCK6 p.Arg249Cys Uncertain significance ★★ ⚠ same residue
DOCK6 c.5939+2T>C Pathogenic ★★ same condition
DOCK6 p.Glu1494Ter Pathogenic ★★ same condition
DOCK6 p.Ala1153Thr Uncertain significance ★★ ⚠ same condition
DOCK6 p.Ala1207Val Uncertain significance ★★ ⚠ same condition
DOCK6 p.Ala1241Thr Uncertain significance ★★ ⚠ same condition
DOCK6 p.Ala1319Val Uncertain significance ★★ ⚠ same condition
DOCK6 p.Ala133Thr 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/dock6-p-arg249his (accessed [today's date]).

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