Is DOCK1 p.Leu931Phe (c.2791C>T) pathogenic?

DOCK1 p.Leu931Phe (c.2791C>T) is classified Uncertain significance in DOCK1 (ClinVar, Single submitter, 1 submitter; last evaluated 2022-01-03). AlphaMissense: likely pathogenic (0.7037); Very rare (popmax 0.000137%); Associated with DOCK1-related disorder.

What condition is associated with DOCK1 p.Leu931Phe (c.2791C>T)?

DOCK1 p.Leu931Phe (c.2791C>T) is associated with DOCK1-related disorder (ClinVar).

How common is DOCK1 p.Leu931Phe (c.2791C>T) in the general population?

DOCK1 p.Leu931Phe (c.2791C>T) is very rare (popmax 0.000137%) (gnomAD).

What do computational predictors say about DOCK1 p.Leu931Phe (c.2791C>T)?

AlphaMissense predicts likely pathogenic (score 0.7037) — an in-silico prediction, not a clinical call.

DOCK1 p.Leu931Phe

c.2791C>T · rs1288540444 · VCV1333365

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely pathogenic

0.7037 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 0.000137%)

Missense predictors

1/2 damaging

AlphaMissense, SaProt · REVEL no call

Conditions

DOCK1-related disorder

Computational evidence

Protein change
AlphaMissense	0.7037	likely pathogenic
REVEL	0.642	indeterminate
SaProt	LLR -9.11	tolerated
⇒ AlphaMissense calls this damaging; SaProt does not; REVEL makes no call.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 5.9	GERP 1.7, phastCons 1
Regional constraint	o/e 0.90	unconstrained · MANE · 321 kb · p 0.017 · regional, not allelic
Overall
CADD	25.0	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 L910F vs ClinVar L931F) — verify the residue.

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.000137%

Overall 0.000137% 2/1,460,626 alleles · very rare

Rarity supports pathogenicity (ACMG PM2); frequency above a disease-specific BA1/BS1 threshold argues against it. A variant frequent in one ancestry group can be near-absent in others, so a single global figure can mislead.

Variant & gene context

Gene: DOCK1
Protein: p.Leu931Phe
Coding: c.2791C>T
MANE Select: NM_001290223
dbSNP: rs1288540444
Type: single nucleotide variant
Location: chr10:127127708 (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

Disease context

DOCK1-related disorder

Similar variants

DOCK1 p.Lys1715Arg Likely benign ⚠ same condition
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

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-leu931phe (accessed [today's date]).

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