Is DOCK8 p.Pro1850Ser (c.5548C>T) pathogenic?

DOCK8 p.Pro1850Ser (c.5548C>T) is classified Uncertain significance in DOCK8 (ClinVar, Multiple submitters, 3 submitters; last evaluated 2025-08-10). AlphaMissense: likely benign (0.1594); Very rare (popmax 0.00161%, nfe); Associated with Inborn genetic diseases.

What condition is associated with DOCK8 p.Pro1850Ser (c.5548C>T)?

DOCK8 p.Pro1850Ser (c.5548C>T) is associated with Inborn genetic diseases, hyper-IgE recurrent infection syndrome 3, autosomal recessive (ClinVar).

How common is DOCK8 p.Pro1850Ser (c.5548C>T) in the general population?

DOCK8 p.Pro1850Ser (c.5548C>T) is very rare (popmax 0.00161%, nfe) (gnomAD).

What do computational predictors say about DOCK8 p.Pro1850Ser (c.5548C>T)?

AlphaMissense predicts likely benign (score 0.1594) — an in-silico prediction, not a clinical call.

DOCK8 p.Pro1850Ser

c.5548C>T · rs369327204 · VCV953407

Uncertain significance Multiple submitters

Classification

Uncertain significance

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 3 submitters

AlphaMissense

likely benign

0.1594 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 0.00161%, nfe)

Missense predictors

0/3 damaging

AlphaMissense, REVEL, SaProt

Conditions

Inborn genetic diseases

Computational evidence

Protein change
AlphaMissense	0.1594	likely benign
REVEL	0.257	benign-leaning
SaProt	LLR -9.83	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 2.6, phastCons 1
Regional constraint	o/e 1.15	unconstrained · MANE · 235 kb · p 6.4e-14 · regional, not allelic
Overall
CADD	23.8	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 0.00161% European (non-Finnish) · 19/1,179,996 alleles

Filtering AF 0.00103% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.00083%

Overall 0.00118% 19/1,613,914 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: DOCK8
Protein: p.Pro1850Ser
Coding: c.5548C>T
MANE Select: NM_203447
dbSNP: rs369327204
Type: single nucleotide variant
Location: chr9:443484 (GRCh38)
Gene constraint: LOEUF 0.622 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 75.17
Residue 1850: 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

Also linked: hyper-IgE recurrent infection syndrome 3, autosomal recessive

Similar variants

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.Ala13Pro Uncertain significance ★★ ⚠ same condition
DOCK8 p.Ala1579Gly Uncertain significance ★★ ⚠ same condition
DOCK8 p.Ala1736Val Uncertain significance ★★ ⚠ same condition
DOCK8 p.Ala1761Val 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-pro1850ser (accessed [today's date]).

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