Is DOK1 p.Arg207Pro (c.620G>C) pathogenic?

DOK1 p.Arg207Pro (c.620G>C) is classified Uncertain significance in DOK1 (ClinVar, Single submitter, 1 submitter; last evaluated 2025-08-31). AlphaMissense: likely pathogenic (0.9955); Absent from gnomAD v4.1.

How common is DOK1 p.Arg207Pro (c.620G>C) in the general population?

DOK1 p.Arg207Pro (c.620G>C) is absent from gnomAD v4.1 (gnomAD).

What do computational predictors say about DOK1 p.Arg207Pro (c.620G>C)?

AlphaMissense predicts likely pathogenic (score 0.9955) — an in-silico prediction, not a clinical call.

DOK1 p.Arg207Pro

c.620G>C · VCV4244126

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely pathogenic

0.9955 · ACMG-weighted

gnomAD v4.1

Absent

absent from gnomAD v4.1

Missense predictors

3/3 damaging

AlphaMissense, REVEL, SaProt

Computational evidence

Protein change
AlphaMissense	0.9955	likely pathogenic · top 2% in DOK1
REVEL	0.844	moderately pathogenic-leaning
SaProt	LLR -13.56	damaging
⇒ AlphaMissense, REVEL and SaProt all call this damaging.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 9.8	GERP 1.4, phastCons 1
Regional constraint	o/e 0.95	unconstrained · MANE · 2,356 bp · p 0.23 · regional, not allelic
Overall
CADD	31.0	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: DOK1
Protein: p.Arg207Pro
Coding: c.620G>C
MANE Select: NM_001381
Type: single nucleotide variant
Location: chr2:74556059 (GRCh38)
Gene constraint: LOEUF 0.74 · pLI 0.01 (gnomAD)
Structure: AlphaFold pLDDT 68.24 · 1 PDB
Residue 207: the irs-type ptb domain; a β-strand

Full DOK1 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Similar variants

LOXL3 p.Ala98Thr Uncertain significance ★★ ⚠ same type
LOXL3 p.Arg106Cys Uncertain significance ★★ ⚠ same type
LOXL3 p.Arg148Ser Uncertain significance ★★ ⚠ same type
LOXL3 p.Arg179Ile Uncertain significance ★★ ⚠ same type
LOXL3 p.Arg231Trp Uncertain significance ★★ ⚠ same type
LOXL3 p.Arg2Gln Uncertain significance ★★ ⚠ same type
LOXL3 p.Arg43Gln Uncertain significance ★★ ⚠ same type
LOXL3 p.Arg43Trp 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/dok1-p-arg207pro (accessed [today's date]).

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