Is DOCK6 p.Val714Met (c.2140G>A) pathogenic?

DOCK6 p.Val714Met (c.2140G>A) is classified Benign/Likely benign in DOCK6 (ClinVar, Multiple submitters, 4 submitters; last evaluated 2025-07-30). AlphaMissense: likely benign (0.1773); Rare (popmax 0.596%, sas).

How common is DOCK6 p.Val714Met (c.2140G>A) in the general population?

DOCK6 p.Val714Met (c.2140G>A) is rare (popmax 0.596%, sas) (gnomAD).

What do computational predictors say about DOCK6 p.Val714Met (c.2140G>A)?

AlphaMissense predicts likely benign (score 0.1773) — an in-silico prediction, not a clinical call.

DOCK6 p.Val714Met

c.2140G>A · rs549146148 · VCV2166284

Benign/Likely benign Multiple submitters

Classification

Benign/Likely benign

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 4 submitters

AlphaMissense

likely benign

0.1773 · ACMG-weighted

gnomAD v4.1

Rare

rare (popmax 0.596%, sas)

Missense predictors

1/3 damaging

AlphaMissense, REVEL, SaProt

Computational evidence

Protein change
AlphaMissense	0.1773	likely benign
REVEL	0.08	moderately benign-leaning
SaProt	LLR -10.26	damaging
⇒ SaProt calls this damaging; AlphaMissense and REVEL do not.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 1.8	GERP 0.42, phastCons 0.15
Regional constraint	o/e 0.92	unconstrained · MANE · 63 kb · p 1.8e-05 · regional, not allelic
Overall
CADD	19.95	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 0.596% South Asian · 502/84,182 alleles

Filtering AF 0.553% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.536%

Overall 0.0337% 524/1,554,026 alleles · rare

Ancestry group	Frequency	1 in
South Asiangrpmax	0.596%	168
Remaining individualsnot grpmax-eligible	0.0249%	4,015
Middle Eastern	0.0167%	5,992
East Asian	0.00487%	20,549
African / African-American	0.00137%	73,210
European (non-Finnish)	0.000261%	382,933

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.Val714Met
Coding: c.2140G>A
MANE Select: NM_020812
dbSNP: rs549146148
Type: single nucleotide variant
Location: chr19:11236813 (GRCh38)
Gene constraint: LOEUF 0.87 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 77.78 · 7 PDB
Residue 714: the c2 dock-type domain

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

Similar variants

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
DOCK6 p.Glu1494Ter 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-val714met (accessed [today's date]).

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