Is DOCK6 p.Val1260Met (c.3778G>A) pathogenic?

DOCK6 p.Val1260Met (c.3778G>A) is classified Conflicting classifications of pathogenicity in DOCK6 (ClinVar, Conflicting submitters, 2 submitters; last evaluated 2024-11-05). AlphaMissense: ambiguous (0.5589); Ultra-rare (popmax 0.0867%, sas); Associated with Inborn genetic diseases.

What condition is associated with DOCK6 p.Val1260Met (c.3778G>A)?

DOCK6 p.Val1260Met (c.3778G>A) is associated with Inborn genetic diseases (ClinVar).

How common is DOCK6 p.Val1260Met (c.3778G>A) in the general population?

DOCK6 p.Val1260Met (c.3778G>A) is ultra-rare (popmax 0.0867%, sas) (gnomAD).

What do computational predictors say about DOCK6 p.Val1260Met (c.3778G>A)?

AlphaMissense predicts ambiguous (score 0.5589) — an in-silico prediction, not a clinical call.

DOCK6 p.Val1260Met

c.3778G>A · rs576108168 · VCV3085076

Conflicting classifications of pathogenicity Conflicting submitters

Classification

Conflicting classifications of pathogenicity

ClinVar

Review

Conflicting submitters ★☆☆☆

ClinVar · 2 submitters

AlphaMissense

ambiguous

0.5589 · ACMG-weighted

gnomAD v4.1

Rare

ultra-rare (popmax 0.0867%, sas)

Conditions

Inborn genetic diseases

Computational evidence

Protein change
AlphaMissense	0.5589	ambiguous
REVEL	0.334	indeterminate
SaProt	LLR -12.67	damaging
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 4.9	GERP 2.6, phastCons 1
Regional constraint	o/e 0.92	unconstrained · MANE · 63 kb · p 1.8e-05 · regional, not allelic
Overall
CADD	25.9	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 0.0867% South Asian · 79/91,092 alleles

Filtering AF 0.0713% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.0656%

Overall 0.00521% 84/1,613,634 alleles · ultra-rare

Ancestry group	Frequency	1 in
South Asiangrpmax	0.0867%	1,153
Remaining individualsnot grpmax-eligible	0.0048%	20,827
African / African-American	0.00133%	75,062
European (non-Finnish)	8.48e-05%	1,179,892

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.Val1260Met
Coding: c.3778G>A
MANE Select: NM_020812
dbSNP: rs576108168
Type: single nucleotide variant
Location: chr19:11217030 (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

Inborn genetic diseases — disease report on Sugi Atlas → Associated genes, phenotypes, clinical trials & treatments

Similar variants

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
DOCK6 p.Ala1481Thr 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-val1260met (accessed [today's date]).

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