Is IP6K3 p.Pro301His (c.902C>A) pathogenic?

IP6K3 p.Pro301His (c.902C>A) is classified Uncertain significance in IP6K3 (ClinVar, Single submitter, 1 submitter; last evaluated 2023-05-17). AlphaMissense: ambiguous (0.3852); Very rare (popmax 8.47e-05%, nfe).

How common is IP6K3 p.Pro301His (c.902C>A) in the general population?

IP6K3 p.Pro301His (c.902C>A) is very rare (popmax 8.47e-05%, nfe) (gnomAD).

What do computational predictors say about IP6K3 p.Pro301His (c.902C>A)?

AlphaMissense predicts ambiguous (score 0.3852) — an in-silico prediction, not a clinical call.

IP6K3 p.Pro301His

c.902C>A · rs2533249885 · VCV2524825

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

ambiguous

0.3852 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 8.47e-05%, nfe)

Computational evidence

Protein change
AlphaMissense	0.3852	ambiguous
REVEL	0.372	indeterminate
SaProt	LLR -11.41	damaging
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 12	GERP 2.3, phastCons 1
Regional constraint	o/e 0.89	unconstrained · MANE · 13 kb · p 0.014 · regional, not allelic
Overall
CADD	28.5	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

Grpmax group 8.47e-05% European (non-Finnish) · 1/1,180,028 alleles

Overall 6.2e-05% 1/1,614,136 alleles · very rare exomes 1/1,461,874 · genomes 0/152,262 · joint denominator

Rarity supports pathogenicity (ACMG PM2); frequency above a disease-specific BA1/BS1 threshold argues against it. A variant frequent in one ancestry group can be near-absent in others, so a single global figure can mislead.

Variant & gene context

Gene: IP6K3
Protein: p.Pro301His
Coding: c.902C>A
MANE Select: NM_054111
dbSNP: rs2533249885
Type: single nucleotide variant
Location: chr6:33723051 (GRCh38)
Gene constraint: LOEUF 1.028 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 76.40

Full IP6K3 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Similar variants

IP6K3 p.Gly26Arg Uncertain significance ★★ ⚠ same type
IP6K3 p.Ala124Asp Uncertain significance ★ ⚠ same type
IP6K3 p.Ala129Val Uncertain significance ★ ⚠ same type
IP6K3 p.Ala233Pro Uncertain significance ★ ⚠ same type
IP6K3 p.Ala7Thr Uncertain significance ★ ⚠ same type
IP6K3 p.Ala9Val Uncertain significance ★ ⚠ same type
IP6K3 p.Arg133Ser Uncertain significance ★ ⚠ same type
IP6K3 p.Arg185Cys 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/ip6k3-p-pro301his (accessed [today's date]).

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