Is DOCK6 p.Pro1348= (c.4044G>A) pathogenic?

DOCK6 p.Pro1348= (c.4044G>A) is classified Benign in DOCK6 (ClinVar, Multiple submitters, 7 submitters; last evaluated 2026-02-03). Common (popmax 61%, nfe) — too common for a highly-penetrant pathogenic allele; Associated with Adams-Oliver syndrome 2.

What condition is associated with DOCK6 p.Pro1348= (c.4044G>A)?

DOCK6 p.Pro1348= (c.4044G>A) is associated with Adams-Oliver syndrome 2 (ClinVar).

DOCK6 p.Pro1348=

Q: How common is DOCK6 p.Pro1348= (c.4044G>A) in the general population?

DOCK6 p.Pro1348= (c.4044G>A) is common (popmax 61%, nfe) — too common for a highly-penetrant pathogenic allele (gnomAD).

c.4044G>A · rs2304154 · VCV518286

Benign Multiple submitters

Classification

Benign

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 7 submitters

gnomAD v4.1

Common

common (popmax 61%, nfe) — too common for a highly-penetrant pathogenic allele

Conditions

Adams-Oliver syndrome 2

Computational evidence

Protein change
Missense predictors do not apply to this variant type; conservation carries the signal.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 0.13	GERP -3.9, phastCons 0.94
Overall
CADD	10.07	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 61% European (non-Finnish) · 718,755/1,177,520 alleles

Filtering AF 60.9% ClinGen BA1/BS1 input FAF95, joint · FAF99 60.9%

Overall 58.1% 934,548/1,609,714 alleles · common

Ancestry group	Frequency	1 in
Ashkenazi Jewishnot grpmax-eligible	65.1%	2
European (non-Finnish)grpmax	61%	2
Middle Eastern	61%	2
Remaining individualsnot grpmax-eligible	56.6%	2
Finnishnot grpmax-eligible	55%	2
Admixed American	54.8%	2
South Asian	50%	2
East Asian	50%	2
Amishnot grpmax-eligible	38.3%	3
African / African-American	29.2%	3

Ashkenazi Jewish shows a higher raw frequency than the grpmax group above it. gnomAD excludes bottlenecked groups — Finnish, Ashkenazi Jewish, Amish and “Remaining individuals” — from grpmax, because founder effects make their frequencies unrepresentative for filtering. The table is sorted by frequency, so an excluded group can sit above the grpmax row.

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.Pro1348=
Coding: c.4044G>A
MANE Select: NM_020812
dbSNP: rs2304154
Type: single nucleotide variant
Location: chr19:11215449 (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

Disease context

Adams-Oliver syndrome 2 — disease report on Sugi Atlas → Associated genes, phenotypes, clinical trials & treatments

Similar variants

DOCK6 c.5939+2T>C Pathogenic ★★ same condition
DOCK6 c.807-1G>A Likely pathogenic ★★ same condition
DOCK6 p.Arg1526Ter Pathogenic/Likely pathogenic ★★ same condition
DOCK6 p.Arg184Ter Pathogenic/Likely pathogenic ★★ same condition
DOCK6 p.Arg488Ter Pathogenic/Likely pathogenic ★★ same condition
DOCK6 p.Gln1188Ter Pathogenic/Likely pathogenic ★★ same condition
DOCK6 p.Tyr129Ter Pathogenic/Likely pathogenic ★★ same condition
DOCK6 p.Tyr235Ter Pathogenic/Likely pathogenic ★★ 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-pro1348 (accessed [today's date]).

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