Is DOCK1 p.Ala1689Ser (c.5065G>T) pathogenic?

DOCK1 p.Ala1689Ser (c.5065G>T) is classified Uncertain significance in DOCK1 (ClinVar, Single submitter, 1 submitter; last evaluated 2024-06-26). AlphaMissense: likely benign (0.0802); Absent from gnomAD v4.1.

How common is DOCK1 p.Ala1689Ser (c.5065G>T) in the general population?

DOCK1 p.Ala1689Ser (c.5065G>T) is absent from gnomAD v4.1 (gnomAD).

What do computational predictors say about DOCK1 p.Ala1689Ser (c.5065G>T)?

AlphaMissense predicts likely benign (score 0.0802) — an in-silico prediction, not a clinical call.

DOCK1 p.Ala1689Ser

c.5065G>T · VCV3504317

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.0802 · ACMG-weighted

gnomAD v4.1

Absent

absent from gnomAD v4.1

Missense predictors

0/3 damaging

AlphaMissense, REVEL, SaProt

Computational evidence

Protein change
AlphaMissense	0.0802	likely benign
REVEL	0.054	moderately benign-leaning
SaProt	LLR -5.26	tolerated
⇒ AlphaMissense, REVEL and SaProt all call this tolerated.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 6.3	GERP 0.6, phastCons 1
Regional constraint	o/e 0.91	unconstrained · MANE · 32 kb · p 0.07 · regional, not allelic
Overall
CADD	18.41	PHRED · no single calibrated threshold — expert panels disagree

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

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

⚠ Isoform check: AlphaMissense numbered on a different transcript (AM A1668S vs ClinVar A1689S) — 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.Ala1689Ser
Coding: c.5065G>T
MANE Select: NM_001290223
Type: single nucleotide variant
Location: chr10:127439031 (GRCh38)
Gene constraint: LOEUF 0.637 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 79.63 · 1 PDB
Residue 1689: the 'disordered' region; the 'phosphoinositide-binding' 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.Ala280Thr Uncertain significance ★ ⚠ same type
DOCK1 p.Ala551Thr 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-ala1689ser (accessed [today's date]).

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