Is DOCK6 p.Arg1041His (c.3122G>A) pathogenic?

DOCK6 p.Arg1041His (c.3122G>A) is classified Uncertain significance in DOCK6 (ClinVar, Single submitter, 1 submitter; last evaluated 2022-06-23). AlphaMissense: ambiguous (0.4497); Very rare (popmax 0.0045%, eas).

How common is DOCK6 p.Arg1041His (c.3122G>A) in the general population?

DOCK6 p.Arg1041His (c.3122G>A) is very rare (popmax 0.0045%, eas) (gnomAD).

What do computational predictors say about DOCK6 p.Arg1041His (c.3122G>A)?

AlphaMissense predicts ambiguous (score 0.4497) — an in-silico prediction, not a clinical call.

DOCK6 p.Arg1041His

c.3122G>A · rs764151265 · VCV2156787

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

ambiguous

0.4497 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 0.0045%, eas)

Computational evidence

Protein change
AlphaMissense	0.4497	ambiguous
REVEL	0.344	indeterminate
SaProt	LLR -3.75	tolerated
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 7.7	GERP 2.6, phastCons 1
Regional constraint	o/e 0.92	unconstrained · MANE · 63 kb · p 1.8e-05 · regional, not allelic
Overall
CADD	28.0	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 0.0045% East Asian · 2/44,444 alleles

Filtering AF 0.00089% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.000541%

Overall 0.00125% 20/1,603,476 alleles · very rare

Ancestry group	Frequency	1 in
East Asiangrpmax	0.0045%	22,222
South Asian	0.00335%	29,841
Remaining individualsnot grpmax-eligible	0.00161%	62,148
European (non-Finnish)	0.00119%	83,959

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.Arg1041His
Coding: c.3122G>A
MANE Select: NM_020812
dbSNP: rs764151265
Type: single nucleotide variant
Location: chr19:11222853 (GRCh38)
Gene constraint: LOEUF 0.87 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 77.78 · 7 PDB

Full DOCK6 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Similar variants

DOCK6 p.Arg1041Gly Uncertain significance ★ ⚠ same residue
DOCK6 c.4491+1G>A Pathogenic ★★ same type
DOCK6 c.5939+2T>C Pathogenic ★★ same type
DOCK6 c.807-1G>A Likely pathogenic ★★ same type
DOCK6 p.Arg1526Ter Pathogenic/Likely pathogenic ★★ same type
DOCK6 p.Arg184Ter Pathogenic/Likely pathogenic ★★ same type
DOCK6 p.Arg488Ter Pathogenic/Likely pathogenic ★★ same type
DOCK6 p.Gln1188Ter Pathogenic/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/dock6-p-arg1041his (accessed [today's date]).

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