Is DOK2 p.Phe211Val (c.631T>G) pathogenic?

DOK2 p.Phe211Val (c.631T>G) is classified Uncertain significance in DOK2 (ClinVar, Single submitter, 1 submitter; last evaluated 2023-12-15). AlphaMissense: likely pathogenic (0.7362); Absent from gnomAD v4.1.

How common is DOK2 p.Phe211Val (c.631T>G) in the general population?

DOK2 p.Phe211Val (c.631T>G) is absent from gnomAD v4.1 (gnomAD).

What do computational predictors say about DOK2 p.Phe211Val (c.631T>G)?

AlphaMissense predicts likely pathogenic (score 0.7362) — an in-silico prediction, not a clinical call.

DOK2 p.Phe211Val

c.631T>G · rs1809770944 · VCV3085169

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely pathogenic

0.7362 · ACMG-weighted

gnomAD v4.1

Absent

absent from gnomAD v4.1

Missense predictors

3/3 damaging

AlphaMissense, REVEL, SaProt

Computational evidence

Protein change
AlphaMissense	0.7362	likely pathogenic
REVEL	0.824	moderately pathogenic-leaning
SaProt	LLR -10.96	damaging
⇒ AlphaMissense, REVEL and SaProt all call this damaging.
Splicing
SpliceAI	Δ0.29	acceptor loss, 10 bp away · masked 0 · deltas
Constraint at this position
Conservation	phyloP 11	GERP 1.6, phastCons 1
Regional constraint	o/e 1.22	unconstrained · MANE · 4,287 bp · p 1.6e-07 · regional, not allelic
Overall
CADD	27.4	PHRED · no single calibrated threshold — expert panels disagree

ClinVar classifies this uncertain; the computational predictors unanimously lean damaging — a triage signal, not a reclassification

AlphaMissense carries the ACMG weight for missense; REVEL and SaProt are independent agreement signals.

Population frequency

gnomAD v4.1 · exomes + genomes

Absent from gnomAD v4.1. Not observed in any sequenced alleles — a rarity signal (ACMG PM2-supporting), not evidence of pathogenicity on its own.

Variant & gene context

Gene: DOK2
Protein: p.Phe211Val
Coding: c.631T>G
MANE Select: NM_003974
dbSNP: rs1809770944
Type: single nucleotide variant
Location: chr8:21909919 (GRCh38)
Gene constraint: LOEUF 1.838 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 70.72 · 2 PDB
Residue 211: the irs-type ptb domain; a β-strand

Full DOK2 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Similar variants

DOK2 p.Ser394Ala Benign ★★ same type
DOK2 p.Ala113Thr Uncertain significance ★ ⚠ same type
DOK2 p.Ala160Thr Uncertain significance ★ ⚠ same type
DOK2 p.Ala237Val Uncertain significance ★ ⚠ same type
DOK2 p.Ala28Pro Uncertain significance ★ ⚠ same type
DOK2 p.Ala372Val Uncertain significance ★ ⚠ same type
DOK2 p.Ala379Val Uncertain significance ★ ⚠ same type
DOK2 p.Ala37Ser 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/dok2-p-phe211val (accessed [today's date]).

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