Is DOCK1 p.Leu96Val (c.286C>G) pathogenic?

DOCK1 p.Leu96Val (c.286C>G) is classified Uncertain significance in DOCK1 (ClinVar, Single submitter, 1 submitter; last evaluated 2023-02-08). AlphaMissense: ambiguous (0.5027); Absent from gnomAD v4.1.

How common is DOCK1 p.Leu96Val (c.286C>G) in the general population?

DOCK1 p.Leu96Val (c.286C>G) is absent from gnomAD v4.1 (gnomAD).

What do computational predictors say about DOCK1 p.Leu96Val (c.286C>G)?

AlphaMissense predicts ambiguous (score 0.5027) — an in-silico prediction, not a clinical call.

DOCK1 p.Leu96Val

c.286C>G · rs2494807477 · VCV2482371

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

ambiguous

0.5027 · ACMG-weighted

gnomAD v4.1

Absent

absent from gnomAD v4.1

Computational evidence

Protein change
AlphaMissense	0.5027	ambiguous
REVEL	0.307	indeterminate
SaProt	LLR -11.18	damaging
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 4.8	GERP 2.7, phastCons 1
Regional constraint	o/e 0.89	unconstrained · MANE · 93 kb · p 0.089 · regional, not allelic
Overall
CADD	25.7	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

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.Leu96Val
Coding: c.286C>G
MANE Select: NM_001290223
dbSNP: rs2494807477
Type: single nucleotide variant
Location: chr10:126987579 (GRCh38)
Gene constraint: LOEUF 0.637 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 79.63 · 1 PDB

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-leu96val (accessed [today's date]).

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