Is DOCK6 p.Val1621Ala (c.4862T>C) pathogenic?

DOCK6 p.Val1621Ala (c.4862T>C) is classified Conflicting classifications of pathogenicity in DOCK6 (ClinVar, Conflicting submitters, 8 submitters; last evaluated 2026-01-09). AlphaMissense: likely pathogenic (0.7784); Rare (popmax 0.419%, sas).

How common is DOCK6 p.Val1621Ala (c.4862T>C) in the general population?

DOCK6 p.Val1621Ala (c.4862T>C) is rare (popmax 0.419%, sas) (gnomAD).

What do computational predictors say about DOCK6 p.Val1621Ala (c.4862T>C)?

AlphaMissense predicts likely pathogenic (score 0.7784) — an in-silico prediction, not a clinical call.

DOCK6 p.Val1621Ala

c.4862T>C · rs201738818 · VCV289212

Conflicting classifications of pathogenicity Conflicting submitters

Classification

Conflicting classifications of pathogenicity

ClinVar

Review

Conflicting submitters ★☆☆☆

ClinVar · 8 submitters

AlphaMissense

likely pathogenic

0.7784 · ACMG-weighted

gnomAD v4.1

Rare

rare (popmax 0.419%, sas)

Missense predictors

2/2 damaging

AlphaMissense, SaProt · REVEL no call

Computational evidence

Protein change
AlphaMissense	0.7784	likely pathogenic
REVEL	0.385	indeterminate
SaProt	LLR -10.01	damaging
⇒ AlphaMissense and SaProt both call this damaging; REVEL makes no call.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 11	GERP 1.9, phastCons 1
Regional constraint	o/e 0.92	unconstrained · MANE · 63 kb · p 1.8e-05 · regional, not allelic
Overall
CADD	23.3	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 0.419% South Asian · 381/90,866 alleles

Filtering AF 0.385% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.371%

Overall 0.268% 4,314/1,611,170 alleles · rare

Ancestry group	Frequency	1 in
South Asiangrpmax	0.419%	238
European (non-Finnish)	0.312%	320
Remaining individualsnot grpmax-eligible	0.16%	624
Admixed American	0.0753%	1,328
Finnishnot grpmax-eligible	0.073%	1,370
Ashkenazi Jewishnot grpmax-eligible	0.0576%	1,735
African / African-American	0.056%	1,785
Middle Eastern	0.0165%	6,054

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.Val1621Ala
Coding: c.4862T>C
MANE Select: NM_020812
dbSNP: rs201738818
Type: single nucleotide variant
Location: chr19:11208993 (GRCh38)
Gene constraint: LOEUF 0.87 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 77.78 · 7 PDB
Residue 1621: the docker domain

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

Similar variants

DOCK6 p.Val1621Met 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-val1621ala (accessed [today's date]).

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