Is IP6K1 p.Pro378Ser (c.1132C>T) pathogenic?

IP6K1 p.Pro378Ser (c.1132C>T) is classified Uncertain significance in IP6K1 (ClinVar, Single submitter, 1 submitter; last evaluated 2025-01-29). AlphaMissense: likely benign (0.0634); Absent from gnomAD v4.1.

How common is IP6K1 p.Pro378Ser (c.1132C>T) in the general population?

IP6K1 p.Pro378Ser (c.1132C>T) is absent from gnomAD v4.1 (gnomAD).

What do computational predictors say about IP6K1 p.Pro378Ser (c.1132C>T)?

AlphaMissense predicts likely benign (score 0.0634) — an in-silico prediction, not a clinical call.

IP6K1 p.Pro378Ser

c.1132C>T · VCV3860898

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.0634 · ACMG-weighted

gnomAD v4.1

Not reported

no allele count reported in gnomAD v4.1 (AN 1,614,120)

Missense predictors

0/3 damaging

AlphaMissense, REVEL, SaProt

Computational evidence

Protein change
AlphaMissense	0.0634	likely benign
REVEL	0.034	moderately benign-leaning
SaProt	LLR -5.35	tolerated
⇒ AlphaMissense, REVEL and SaProt all call this tolerated.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 4.9	GERP 2.8, phastCons 1
Regional constraint	o/e 0.77	unconstrained · MANE · 463 bp · p 0.0007 · regional, not allelic
Overall
CADD	21.4	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

No allele count reported in gnomAD v4.1 (AN 1,614,120). This is missing data, not an absence: the variant may or may not be present in gnomAD. Rarity (ACMG PM2) and BA1/BS1 cannot be assessed for it.

Variant & gene context

Gene: IP6K1
Protein: p.Pro378Ser
Coding: c.1132C>T
MANE Select: NM_153273
Type: single nucleotide variant
Location: chr3:49727316 (GRCh38)
Gene constraint: LOEUF 0.516 · pLI 0.97 (gnomAD)
Structure: AlphaFold pLDDT 75.39
Residue 378: the 'disordered' region

Full IP6K1 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Similar variants

IP6K1 p.Ala136Val Uncertain significance ★ ⚠ same type
IP6K1 p.Ala369Val Uncertain significance ★ ⚠ same type
IP6K1 p.Ala385Val Uncertain significance ★ ⚠ same type
IP6K1 p.Arg110Trp Uncertain significance ★ ⚠ same type
IP6K1 p.Arg115Cys Uncertain significance ★ ⚠ same type
IP6K1 p.Arg18Gln Uncertain significance ★ ⚠ same type
IP6K1 p.Arg196Cys Uncertain significance ★ ⚠ same type
IP6K1 p.Arg230Gln 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/ip6k1-p-pro378ser (accessed [today's date]).

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