Is DOCK8 p.Ser1029Leu (c.3086C>T) pathogenic?

DOCK8 p.Ser1029Leu (c.3086C>T) is classified Uncertain significance in DOCK8 (ClinVar, Multiple submitters, 2 submitters; last evaluated 2024-07-28). AlphaMissense: likely benign (0.0957); Very rare (popmax 0.00229%, nfe); Associated with Inborn genetic diseases.

What condition is associated with DOCK8 p.Ser1029Leu (c.3086C>T)?

DOCK8 p.Ser1029Leu (c.3086C>T) is associated with Inborn genetic diseases (ClinVar).

How common is DOCK8 p.Ser1029Leu (c.3086C>T) in the general population?

DOCK8 p.Ser1029Leu (c.3086C>T) is very rare (popmax 0.00229%, nfe) (gnomAD).

What do computational predictors say about DOCK8 p.Ser1029Leu (c.3086C>T)?

AlphaMissense predicts likely benign (score 0.0957) — an in-silico prediction, not a clinical call.

DOCK8 p.Ser1029Leu

c.3086C>T · rs776318168 · VCV2959715

Uncertain significance Multiple submitters

Classification

Uncertain significance

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 2 submitters

AlphaMissense

likely benign

0.0957 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 0.00229%, nfe)

Missense predictors

0/3 damaging

AlphaMissense, REVEL, SaProt

Conditions

Inborn genetic diseases

Computational evidence

Protein change
AlphaMissense	0.0957	likely benign
REVEL	0.112	moderately benign-leaning
SaProt	LLR -6.55	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 7.6	GERP 1.7, phastCons 1
Regional constraint	o/e 1.15	unconstrained · MANE · 235 kb · p 6.4e-14 · regional, not allelic
Overall
CADD	25.8	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.

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.00229% European (non-Finnish) · 27/1,180,020 alleles

Filtering AF 0.00157% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.00134%

Overall 0.00186% 30/1,614,012 alleles · very rare

Ancestry group	Frequency	1 in
European (non-Finnish)grpmax	0.00229%	43,704
East Asian	0.00223%	44,882
Finnishnot grpmax-eligible	0.00156%	63,934
South Asian	0.0011%	91,070

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.Ser1029Leu
Coding: c.3086C>T
MANE Select: NM_203447
dbSNP: rs776318168
Type: single nucleotide variant
Location: chr9:396900 (GRCh38)
Gene constraint: LOEUF 0.622 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 75.17

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.Ser1029= 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-ser1029leu (accessed [today's date]).

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