Is DOCK8 p.Pro364Arg (c.1091C>G) pathogenic?

DOCK8 p.Pro364Arg (c.1091C>G) is classified Likely benign in DOCK8 (ClinVar, No assertion criteria, 1 submitter; last evaluated 2019-01-01). AlphaMissense: likely pathogenic (0.946); Absent from gnomAD v4.1; Associated with intellectual disability.

What condition is associated with DOCK8 p.Pro364Arg (c.1091C>G)?

DOCK8 p.Pro364Arg (c.1091C>G) is associated with intellectual disability (ClinVar).

How common is DOCK8 p.Pro364Arg (c.1091C>G) in the general population?

DOCK8 p.Pro364Arg (c.1091C>G) is absent from gnomAD v4.1 (gnomAD).

What do computational predictors say about DOCK8 p.Pro364Arg (c.1091C>G)?

AlphaMissense predicts likely pathogenic (score 0.946) — an in-silico prediction, not a clinical call.

DOCK8 p.Pro364Arg

c.1091C>G · rs781095788 · VCV975224

Likely benign No assertion criteria

Classification

Likely benign

ClinVar

Review

No assertion criteria ☆☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely pathogenic

0.946 · ACMG-weighted

gnomAD v4.1

Absent

absent from gnomAD v4.1

Missense predictors

2/3 damaging

AlphaMissense, REVEL, SaProt

Conditions

intellectual disability

Computational evidence

Protein change
AlphaMissense	0.946	likely pathogenic · top 6% in DOCK8
REVEL	0.725	pathogenic-leaning
SaProt	LLR -3.34	tolerated
⇒ AlphaMissense and REVEL call this damaging; SaProt does not.
Splicing
SpliceAI	<0.2	no splice effect predicted · four deltas, not one · how we know
Constraint at this position
Conservation	phyloP 7.5	GERP 2.8, phastCons 1
Regional constraint	o/e 1.15	unconstrained · MANE · 235 kb · p 6.4e-14 · regional, not allelic
Overall
CADD	26.4	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.Pro364Arg
Coding: c.1091C>G
MANE Select: NM_203447
dbSNP: rs781095788
Type: single nucleotide variant
Location: chr9:332444 (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

intellectual disability — disease report on Sugi Atlas → Associated genes, phenotypes, clinical trials & treatments

Similar variants

DOCK8 p.Pro364Ser Uncertain significance ★★ ⚠ same residue
DOCK8 p.Pro364Thr Uncertain significance ★★ ⚠ same residue
DOCK8 p.Arg398Gln Uncertain significance ★★ same condition
DOCK8 p.Glu917Lys Uncertain significance ★★ ⚠ same condition
DOCK8 p.Thr911Ala Uncertain significance ★★ ⚠ same condition
DOCK8 p.Val530Met Uncertain significance ★★ ⚠ same condition
DOCK8 c.54-1G>T Conflicting classifications of pathogenicity ★ same condition
DOCK8 p.Ala1447Gly 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-pro364arg (accessed [today's date]).

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