Is HOOK2 p.Arg337Pro (c.1010G>C) pathogenic?

HOOK2 p.Arg337Pro (c.1010G>C) is classified Uncertain significance in HOOK2 (ClinVar, Single submitter, 1 submitter; last evaluated 2023-11-03). AlphaMissense: likely pathogenic (0.824); Absent from gnomAD v4.1.

How common is HOOK2 p.Arg337Pro (c.1010G>C) in the general population?

HOOK2 p.Arg337Pro (c.1010G>C) is absent from gnomAD v4.1 (gnomAD).

What do computational predictors say about HOOK2 p.Arg337Pro (c.1010G>C)?

AlphaMissense predicts likely pathogenic (score 0.824) — an in-silico prediction, not a clinical call.

HOOK2 p.Arg337Pro

c.1010G>C · rs757282027 · VCV3106505

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely pathogenic

0.824 · ACMG-weighted

gnomAD v4.1

Absent

absent from gnomAD v4.1

Missense predictors

2/3 damaging

AlphaMissense, REVEL, SaProt

Computational evidence

Protein change
AlphaMissense	0.824	likely pathogenic · top 5% in HOOK2
REVEL	0.221	benign-leaning
SaProt	LLR -13.93	damaging
⇒ AlphaMissense and SaProt call this damaging; REVEL does not.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 4.8	GERP 1.2, phastCons 0.51
Regional constraint	o/e 1.08	unconstrained · MANE · 5,167 bp · p 0.12 · regional, not allelic
Overall
CADD	24.8	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: HOOK2
Protein: p.Arg337Pro
Coding: c.1010G>C
MANE Select: NM_013312
dbSNP: rs757282027
Type: single nucleotide variant
Location: chr19:12769975 (GRCh38)
Gene constraint: LOEUF 1.16 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 82.81
Residue 337: the 'sufficient for interaction with microtubules' region

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

Similar variants

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
HK2 p.Ala387Thr 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-arg337pro (accessed [today's date]).

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