Is DOCK8 p.Ala2Asp (c.5C>A) pathogenic?

DOCK8 p.Ala2Asp (c.5C>A) is classified Uncertain significance in DOCK8 (ClinVar, Single submitter, 1 submitter; last evaluated 2025-06-29). AlphaMissense: likely pathogenic (0.8872); Absent from gnomAD v4.1; Associated with Inborn genetic diseases.

What condition is associated with DOCK8 p.Ala2Asp (c.5C>A)?

DOCK8 p.Ala2Asp (c.5C>A) is associated with Inborn genetic diseases (ClinVar).

How common is DOCK8 p.Ala2Asp (c.5C>A) in the general population?

DOCK8 p.Ala2Asp (c.5C>A) is absent from gnomAD v4.1 (gnomAD).

What do computational predictors say about DOCK8 p.Ala2Asp (c.5C>A)?

AlphaMissense predicts likely pathogenic (score 0.8872) — an in-silico prediction, not a clinical call.

DOCK8 p.Ala2Asp

c.5C>A · VCV4244055

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely pathogenic

0.8872 · ACMG-weighted

gnomAD v4.1

Absent

absent from gnomAD v4.1

Missense predictors

1/3 damaging

AlphaMissense, REVEL, SaProt

Conditions

Inborn genetic diseases

Computational evidence

Protein change
AlphaMissense	0.8872	likely pathogenic
REVEL	0.209	benign-leaning
SaProt	LLR -6.83	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 7.3	GERP 0.81, phastCons 1
Regional constraint	o/e 1.15	unconstrained · MANE · 235 kb · p 6.4e-14 · regional, not allelic
Overall
CADD	26.0	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

Absent from gnomAD v4.1. Not observed in any sequenced alleles — a rarity signal (ACMG PM2-supporting), not evidence of pathogenicity on its own.

Variant & gene context

Gene: DOCK8
Protein: p.Ala2Asp
Coding: c.5C>A
MANE Select: NM_203447
Type: single nucleotide variant
Location: chr9:214981 (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.Ala2Thr Uncertain significance ★ ⚠ same residue
DOCK8 p.Ala2= 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

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-ala2asp (accessed [today's date]).

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