Is DOCK8 p.Pro2001Ala (c.6001C>G) pathogenic?

DOCK8 p.Pro2001Ala (c.6001C>G) is classified Uncertain significance in DOCK8 (ClinVar, Single submitter, 1 submitter; last evaluated 2025-03-26). AlphaMissense: likely pathogenic (0.7041); Very rare (popmax 0.00693%, amr); Associated with Inborn genetic diseases.

What condition is associated with DOCK8 p.Pro2001Ala (c.6001C>G)?

DOCK8 p.Pro2001Ala (c.6001C>G) is associated with Inborn genetic diseases (ClinVar).

How common is DOCK8 p.Pro2001Ala (c.6001C>G) in the general population?

DOCK8 p.Pro2001Ala (c.6001C>G) is very rare (popmax 0.00693%, amr) (gnomAD).

What do computational predictors say about DOCK8 p.Pro2001Ala (c.6001C>G)?

AlphaMissense predicts likely pathogenic (score 0.7041) — an in-silico prediction, not a clinical call.

DOCK8 p.Pro2001Ala

c.6001C>G · VCV4014249

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely pathogenic

0.7041 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 0.00693%, amr)

Missense predictors

2/3 damaging

AlphaMissense, REVEL, SaProt

Conditions

Inborn genetic diseases

Computational evidence

Protein change
AlphaMissense	0.7041	likely pathogenic
REVEL	0.198	benign-leaning
SaProt	LLR -14.62	damaging
⇒ AlphaMissense and SaProt call this damaging; REVEL does not.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 7.6	GERP 2.5, phastCons 1
Regional constraint	o/e 1.05	unconstrained · MANE · 12 kb · p 0.6 · regional, not allelic
Overall
CADD	24.0	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

Grpmax group 0.00693% Admixed American · 4/57,718 alleles

Filtering AF 0.00232% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.00139%

Overall 0.000316% 5/1,582,604 alleles · very rare exomes 5/1,439,540 · genomes 0/143,064 · joint denominator

Ancestry group	Frequency	1 in
Admixed Americangrpmax	0.00693%	14,429
South Asian	0.00111%	89,768

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: DOCK8
Protein: p.Pro2001Ala
Coding: c.6001C>G
MANE Select: NM_203447
Type: single nucleotide variant
Location: chr9:452050 (GRCh38)
Gene constraint: LOEUF 0.622 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 75.17
Residue 2001: the docker domain

Full DOCK8 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Disease context

Inborn genetic diseases — disease report on Sugi Atlas → Associated genes, phenotypes, clinical trials & treatments

Similar variants

DOCK8 p.Pro2001= Likely benign ★ same residue
DOCK8 p.Ala1170Thr Uncertain significance ★★ ⚠ same condition
DOCK8 p.Ala1252Pro Uncertain significance ★★ ⚠ same condition
DOCK8 p.Ala1290Val Uncertain significance ★★ ⚠ same condition
DOCK8 p.Ala1383Gly Uncertain significance ★★ ⚠ same condition
DOCK8 p.Ala1579Gly Uncertain significance ★★ ⚠ same condition
DOCK8 p.Ala1736Val Uncertain significance ★★ ⚠ same condition
DOCK8 p.Ala2037Val Uncertain significance ★★ ⚠ same condition

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/dock8-p-pro2001ala (accessed [today's date]).

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