Is IP6K2 p.Lys286Arg (c.857A>G) pathogenic?

IP6K2 p.Lys286Arg (c.857A>G) is classified Uncertain significance in IP6K2 (ClinVar, Single submitter, 1 submitter; last evaluated 2025-08-31). AlphaMissense: likely benign (0.1001); Absent from gnomAD v4.1.

How common is IP6K2 p.Lys286Arg (c.857A>G) in the general population?

IP6K2 p.Lys286Arg (c.857A>G) is absent from gnomAD v4.1 (gnomAD).

What do computational predictors say about IP6K2 p.Lys286Arg (c.857A>G)?

AlphaMissense predicts likely benign (score 0.1001) — an in-silico prediction, not a clinical call.

IP6K2 p.Lys286Arg

c.857A>G · VCV4276100

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.1001 · ACMG-weighted

gnomAD v4.1

Absent

absent from gnomAD v4.1

Missense predictors

0/2 damaging

AlphaMissense, SaProt · REVEL indeterminate

Computational evidence

Protein change
AlphaMissense	0.1001	likely benign
REVEL	0.337	indeterminate
SaProt	LLR -7.40	tolerated
⇒ AlphaMissense and SaProt both call this tolerated; REVEL is indeterminate.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 6.2	GERP 1.7, phastCons 1
Regional constraint	o/e 0.62	unconstrained · MANE · 7,015 bp · p 5.9e-19 · regional, not allelic
Overall
CADD	22.6	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: IP6K2
Protein: p.Lys286Arg
Coding: c.857A>G
MANE Select: NM_016291
Type: single nucleotide variant
Location: chr3:48688697 (GRCh38)
Gene constraint: LOEUF 0.385 · pLI 1.00 (gnomAD)
Structure: AlphaFold pLDDT 75.92

Full IP6K2 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Similar variants

IP6K2 p.Ala195Gly Uncertain significance ★ ⚠ same type
IP6K2 p.Ala374Val Uncertain significance ★ ⚠ same type
IP6K2 p.Ala57Thr Uncertain significance ★ ⚠ same type
IP6K2 p.Arg133Cys Uncertain significance ★ ⚠ same type
IP6K2 p.Arg133His Uncertain significance ★ ⚠ same type
IP6K2 p.Arg198Gln Uncertain significance ★ ⚠ same type
IP6K2 p.Arg198Trp Uncertain significance ★ ⚠ same type
IP6K2 p.Arg212Cys 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/ip6k2-p-lys286arg (accessed [today's date]).

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