Is DOCK1 p.Pro1783Ser (c.5347C>T) pathogenic?

DOCK1 p.Pro1783Ser (c.5347C>T) is classified Uncertain significance in DOCK1 (ClinVar, Multiple submitters, 2 submitters; last evaluated 2025-04-01). AlphaMissense: likely benign (0.0595); Very rare (popmax 0.00167%, amr).

How common is DOCK1 p.Pro1783Ser (c.5347C>T) in the general population?

DOCK1 p.Pro1783Ser (c.5347C>T) is very rare (popmax 0.00167%, amr) (gnomAD).

What do computational predictors say about DOCK1 p.Pro1783Ser (c.5347C>T)?

AlphaMissense predicts likely benign (score 0.0595) — an in-silico prediction, not a clinical call.

DOCK1 p.Pro1783Ser

c.5347C>T · VCV4014034

Uncertain significance Multiple submitters

Classification

Uncertain significance

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 2 submitters

AlphaMissense

likely benign

0.0595 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 0.00167%, amr)

Missense predictors

0/3 damaging

AlphaMissense, REVEL, SaProt

Computational evidence

Protein change
AlphaMissense	0.0595	likely benign
REVEL	0.03	moderately benign-leaning
SaProt	LLR -6.09	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 2.6	GERP 1.5, phastCons 0.96
Regional constraint	o/e 0.91	unconstrained · MANE · 32 kb · p 0.07 · regional, not allelic
Overall
CADD	10.15	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 P1762S vs ClinVar P1783S) — verify the residue.

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.00167% Admixed American · 1/59,790 alleles

Overall 0.000137% 2/1,459,502 alleles · very rare

Ancestry group	Frequency	1 in
Admixed Americangrpmax	0.00167%	59,790
South Asian	0.00111%	89,994

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.Pro1783Ser
Coding: c.5347C>T
MANE Select: NM_001290223
Type: single nucleotide variant
Location: chr10:127444213 (GRCh38)
Gene constraint: LOEUF 0.637 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 79.63 · 1 PDB
Residue 1783: the 'disordered' region

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

Similar variants

DOCK1 p.Pro1783Leu Uncertain significance ★ ⚠ same residue
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-pro1783ser (accessed [today's date]).

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