Is HOOK2 p.Glu384Asp (c.1152G>T) pathogenic?

HOOK2 p.Glu384Asp (c.1152G>T) is classified Uncertain significance in HOOK2 (ClinVar, Single submitter, 1 submitter; last evaluated 2025-05-23). AlphaMissense: likely benign (0.1486); Absent from gnomAD v4.1.

How common is HOOK2 p.Glu384Asp (c.1152G>T) in the general population?

HOOK2 p.Glu384Asp (c.1152G>T) is absent from gnomAD v4.1 (gnomAD).

What do computational predictors say about HOOK2 p.Glu384Asp (c.1152G>T)?

AlphaMissense predicts likely benign (score 0.1486) — an in-silico prediction, not a clinical call.

HOOK2 p.Glu384Asp

c.1152G>T · VCV4035851

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.1486 · ACMG-weighted

gnomAD v4.1

Absent

absent from gnomAD v4.1

Missense predictors

0/3 damaging

AlphaMissense, REVEL, SaProt

Computational evidence

Protein change
AlphaMissense	0.1486	likely benign
REVEL	0.117	moderately benign-leaning
SaProt	LLR -7.01	tolerated
⇒ AlphaMissense, REVEL and SaProt all call this tolerated.
Splicing
SpliceAI	<0.2	no splice effect predicted · four deltas, not one · how we know
Constraint at this position
Conservation	phyloP 2.2	GERP -1.1, phastCons 1
Regional constraint	o/e 1.08	unconstrained · MANE · 5,167 bp · p 0.12 · regional, not allelic
Overall
CADD	19.21	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

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: HOOK2
Protein: p.Glu384Asp
Coding: c.1152G>T
MANE Select: NM_013312
Type: single nucleotide variant
Location: chr19:12768076 (GRCh38)
Gene constraint: LOEUF 1.16 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 82.81
Residue 384: the 'sufficient for interaction with microtubules' region

Full HOOK2 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Similar variants

HOOK2 p.Glu384Gly Uncertain significance ★ ⚠ same residue
HK2 p.Arg44Cys Uncertain significance ★★ ⚠ same type
HK2 p.Tyr515= Benign ★★ same type
HOOK2 c.519+7G>T Benign ★★ same type
HOOK2 p.Glu657Lys Likely benign ★★ ⚠ same type
HOOK2 p.Val445Leu Benign ★★ same type
HK2 p.Ala352Thr Uncertain significance ★ ⚠ same type
HK2 p.Ala383Thr Uncertain significance ★ ⚠ same type

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/hook2-p-glu384asp (accessed [today's date]).

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