Is DOK6 p.Ser262Cys (c.785C>G) pathogenic?

DOK6 p.Ser262Cys (c.785C>G) is classified Uncertain significance in DOK6 (ClinVar, Single submitter, 1 submitter; last evaluated 2024-01-30). AlphaMissense: likely benign (0.1162); Very rare (popmax 0.0011%, sas).

How common is DOK6 p.Ser262Cys (c.785C>G) in the general population?

DOK6 p.Ser262Cys (c.785C>G) is very rare (popmax 0.0011%, sas) (gnomAD).

What do computational predictors say about DOK6 p.Ser262Cys (c.785C>G)?

AlphaMissense predicts likely benign (score 0.1162) — an in-silico prediction, not a clinical call.

DOK6 p.Ser262Cys

c.785C>G · rs1428870621 · VCV3085199

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.1162 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 0.0011%, sas)

Missense predictors

1/2 damaging

AlphaMissense, SaProt · REVEL no call

Computational evidence

Protein change
AlphaMissense	0.1162	likely benign
REVEL	0.498	indeterminate
SaProt	LLR -11.75	damaging
⇒ SaProt calls this damaging; AlphaMissense does not; REVEL makes no call.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 7.6	GERP 2, phastCons 1
Regional constraint	o/e 1.02	unconstrained · MANE · 84 kb · p 0.8 · regional, not allelic
Overall
CADD	24.6	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 0.0011% South Asian · 1/91,090 alleles

Overall 6.84e-05% 1/1,461,804 alleles · very rare

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: DOK6
Protein: p.Ser262Cys
Coding: c.785C>G
MANE Select: NM_152721
dbSNP: rs1428870621
Type: single nucleotide variant
Location: chr18:69757802 (GRCh38)
Gene constraint: LOEUF 0.692 · pLI 0.02 (gnomAD)
Structure: AlphaFold pLDDT 74.63

Full DOK6 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Similar variants

DOK6 p.Ala129Ser Uncertain significance ★ same type
DOK6 p.Ala226Val Uncertain significance ★ ⚠ same type
DOK6 p.Ala267Thr Uncertain significance ★ ⚠ same type
DOK6 p.Ala304Ser Uncertain significance ★ ⚠ same type
DOK6 p.Arg19Lys Uncertain significance ★ ⚠ same type
DOK6 p.Arg246Gln Uncertain significance ★ ⚠ same type
DOK6 p.Arg246Leu Uncertain significance ★ ⚠ same type
DOK6 p.Arg246Trp Uncertain significance ★ ⚠ 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/dok6-p-ser262cys (accessed [today's date]).

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