Is DOCK1 p.Arg1761Lys (c.5282G>A) pathogenic?

DOCK1 p.Arg1761Lys (c.5282G>A) is classified Uncertain significance in DOCK1 (ClinVar, Single submitter, 1 submitter; last evaluated 2025-05-03). AlphaMissense: likely pathogenic (0.6962); Absent from gnomAD v4.1.

How common is DOCK1 p.Arg1761Lys (c.5282G>A) in the general population?

DOCK1 p.Arg1761Lys (c.5282G>A) is absent from gnomAD v4.1 (gnomAD).

What do computational predictors say about DOCK1 p.Arg1761Lys (c.5282G>A)?

AlphaMissense predicts likely pathogenic (score 0.6962) — an in-silico prediction, not a clinical call.

DOCK1 p.Arg1761Lys

c.5282G>A · VCV4014039

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely pathogenic

0.6962 · ACMG-weighted

gnomAD v4.1

Absent

absent from gnomAD v4.1

Missense predictors

1/3 damaging

AlphaMissense, REVEL, SaProt

Computational evidence

Protein change
AlphaMissense	0.6962	likely pathogenic
REVEL	0.192	benign-leaning
SaProt	LLR -7.32	tolerated
⇒ AlphaMissense calls this damaging; REVEL and SaProt do not.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 12	GERP 1.5, phastCons 1
Regional constraint	o/e 0.91	unconstrained · MANE · 32 kb · p 0.07 · regional, not allelic
Overall
CADD	26.8	PHRED · no single calibrated threshold — expert panels disagree

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

⚠ Isoform check: AlphaMissense numbered on a different transcript (AM R1740K vs ClinVar R1761K) — verify the residue.

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: DOCK1
Protein: p.Arg1761Lys
Coding: c.5282G>A
MANE Select: NM_001290223
Type: single nucleotide variant
Location: chr10:127444148 (GRCh38)
Gene constraint: LOEUF 0.637 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 79.63 · 1 PDB
Residue 1761: a modified residue (phosphoserine); the 'disordered' region

Full DOCK1 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Similar variants

DOCK1 p.Pro1783Ser Uncertain significance ★★ ⚠ same type
DOCK1 p.Ala1185Thr Uncertain significance ★ ⚠ same type
DOCK1 p.Ala151Thr Uncertain significance ★ ⚠ same type
DOCK1 p.Ala1578Ser Uncertain significance ★ ⚠ same type
DOCK1 p.Ala1590Gly Uncertain significance ★ ⚠ same type
DOCK1 p.Ala1620Val Uncertain significance ★ ⚠ same type
DOCK1 p.Ala1689Ser Uncertain significance ★ ⚠ same type
DOCK1 p.Ala280Thr 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/dock1-p-arg1761lys (accessed [today's date]).

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