Is DOCK6 p.Thr1402Met (c.4205C>T) pathogenic?

DOCK6 p.Thr1402Met (c.4205C>T) is classified Benign/Likely benign in DOCK6 (ClinVar, Multiple submitters, 8 submitters; last evaluated 2026-01-21). AlphaMissense: likely benign (0.1647); Low-frequency (popmax 1.31%, afr).

How common is DOCK6 p.Thr1402Met (c.4205C>T) in the general population?

DOCK6 p.Thr1402Met (c.4205C>T) is low-frequency (popmax 1.31%, afr) (gnomAD).

What do computational predictors say about DOCK6 p.Thr1402Met (c.4205C>T)?

AlphaMissense predicts likely benign (score 0.1647) — an in-silico prediction, not a clinical call.

DOCK6 p.Thr1402Met

c.4205C>T · rs147554257 · VCV377033

Benign/Likely benign Multiple submitters

Classification

Benign/Likely benign

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 8 submitters

AlphaMissense

likely benign

0.1647 · ACMG-weighted

gnomAD v4.1

Rare

low-frequency (popmax 1.31%, afr)

Missense predictors

0/3 damaging

AlphaMissense, REVEL, SaProt

Computational evidence

Protein change
AlphaMissense	0.1647	likely benign
REVEL	0.277	benign-leaning
SaProt	LLR -9.96	tolerated
⇒ AlphaMissense, REVEL and SaProt all call this tolerated.
Splicing
SpliceAI	<0.2	all four deltas below 0.2 · G>T here scores Δ0.78 · evaluated, not missing
Constraint at this position
Conservation	phyloP 12	GERP 2.4, phastCons 1
Regional constraint	o/e 0.92	unconstrained · MANE · 63 kb · p 1.8e-05 · regional, not allelic
Overall
CADD	28.1	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 1.31% African / African-American · 983/75,040 alleles

Filtering AF 1.24% ClinGen BA1/BS1 input FAF95, joint · FAF99 1.21%

Overall 0.0713% 1,151/1,613,746 alleles · low-frequency

Ancestry group	Frequency	1 in
African / African-Americangrpmax	1.31%	76
Admixed American	0.11%	909
Remaining individualsnot grpmax-eligible	0.0912%	1,096
Middle Eastern	0.0495%	2,021
South Asian	0.0296%	3,373
European (non-Finnish)	0.00127%	78,660

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.Thr1402Met
Coding: c.4205C>T
MANE Select: NM_020812
dbSNP: rs147554257
Type: single nucleotide variant
Location: chr19:11214408 (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.Thr1402= Likely benign ★ 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-thr1402met (accessed [today's date]).

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