Is DOCK1 p.Arg1875Cys (c.5623C>T) pathogenic?

DOCK1 p.Arg1875Cys (c.5623C>T) is classified Uncertain significance in DOCK1 (ClinVar, Single submitter, 1 submitter; last evaluated 2023-06-29). AlphaMissense: likely pathogenic (0.73); Very rare (popmax 0.00172%, amr).

How common is DOCK1 p.Arg1875Cys (c.5623C>T) in the general population?

DOCK1 p.Arg1875Cys (c.5623C>T) is very rare (popmax 0.00172%, amr) (gnomAD).

What do computational predictors say about DOCK1 p.Arg1875Cys (c.5623C>T)?

AlphaMissense predicts likely pathogenic (score 0.73) — an in-silico prediction, not a clinical call.

DOCK1 p.Arg1875Cys

c.5623C>T · rs781421126 · VCV2608093

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely pathogenic

0.73 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 0.00172%, amr)

Missense predictors

1/3 damaging

AlphaMissense, REVEL, SaProt

Computational evidence

Protein change
AlphaMissense	0.73	likely pathogenic
REVEL	0.181	moderately benign-leaning
SaProt	LLR -9.49	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 7.5	GERP 1.2, phastCons 1
Regional constraint	o/e 0.91	unconstrained · MANE · 32 kb · p 0.07 · regional, not allelic
Overall
CADD	32.0	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 R1854C vs ClinVar R1875C) — verify the residue.

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.00172% Admixed American · 1/58,190 alleles

Filtering AF 2.8e-05% ClinGen BA1/BS1 input FAF95, joint · FAF99 1.1e-05%

Overall 0.000207% 3/1,446,702 alleles · very rare

Ancestry group	Frequency	1 in
Admixed Americangrpmax	0.00172%	58,190
European (non-Finnish)	0.000171%	586,404

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.Arg1875Cys
Coding: c.5623C>T
MANE Select: NM_001290223
dbSNP: rs781421126
Type: single nucleotide variant
Location: chr10:127451389 (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.Arg1875His Uncertain significance ★ ⚠ same residue
DOCK1 p.Arg1875Leu Uncertain significance ★ ⚠ same residue
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

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-arg1875cys (accessed [today's date]).

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