Is PI4KB p.Val37Ile (c.109G>A) pathogenic?

PI4KB p.Val37Ile (c.109G>A) is classified Uncertain significance in PI4KB (ClinVar, Single submitter, 1 submitter; last evaluated 2025-04-14). AlphaMissense: likely benign (0.0777); Very rare (popmax 0.00374%, nfe).

How common is PI4KB p.Val37Ile (c.109G>A) in the general population?

PI4KB p.Val37Ile (c.109G>A) is very rare (popmax 0.00374%, nfe) (gnomAD).

What do computational predictors say about PI4KB p.Val37Ile (c.109G>A)?

AlphaMissense predicts likely benign (score 0.0777) — an in-silico prediction, not a clinical call.

PI4KB p.Val37Ile

c.109G>A · VCV3931979

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.0777 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 0.00374%, nfe)

Missense predictors

0/3 damaging

AlphaMissense, REVEL, SaProt

Computational evidence

Protein change
AlphaMissense	0.0777	likely benign
REVEL	0.03	moderately benign-leaning
SaProt	LLR -7.22	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 2.7	GERP -0.53, phastCons 1
Regional constraint	o/e 0.79	unconstrained · MANE · 8,680 bp · p 2.7e-05 · regional, not allelic
Overall
CADD	17.73	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

Grpmax group 0.00374% European (non-Finnish) · 44/1,177,240 alleles

Filtering AF 0.00283% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.00252%

Overall 0.00286% 46/1,608,574 alleles · very rare

Ancestry group	Frequency	1 in
European (non-Finnish)grpmax	0.00374%	26,755
Remaining individualsnot grpmax-eligible	0.00321%	31,125

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: PI4KB
Protein: p.Val37Ile
Coding: c.109G>A
MANE Select: NM_001369623
Type: single nucleotide variant
Location: chr1:151316373 (GRCh38)
Gene constraint: LOEUF 0.421 · pLI 1.00 (gnomAD)
Structure: AlphaFold pLDDT 72.97 · 20 PDB
Residue 37: the pik helical domain

Full PI4KB gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Similar variants

PI4KB p.Val37= Likely benign ★ same residue
PI4KB p.Ile312Val Uncertain significance ★★ ⚠ same type
PI4KB p.Tyr175Cys Uncertain significance ★★ ⚠ same type
PI4KB c.-17G>A Uncertain significance ★ same type
PI4KB c.-6G>T Uncertain significance ★ same type
PI4KB p.Ala106Val Uncertain significance ★ ⚠ same type
PI4KB p.Ala605Gly Uncertain significance ★ ⚠ same type
PI4KB p.Ala67Val 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/pi4kb-p-val37ile (accessed [today's date]).

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