Is PI4KB p.Val66Met (c.196G>A) pathogenic?

PI4KB p.Val66Met (c.196G>A) is classified Uncertain significance in PI4KB (ClinVar, Single submitter, 1 submitter; last evaluated 2025-11-26). AlphaMissense: likely benign (0.0789); Very rare (popmax 0.0011%, nfe).

How common is PI4KB p.Val66Met (c.196G>A) in the general population?

PI4KB p.Val66Met (c.196G>A) is very rare (popmax 0.0011%, nfe) (gnomAD).

What do computational predictors say about PI4KB p.Val66Met (c.196G>A)?

AlphaMissense predicts likely benign (score 0.0789) — an in-silico prediction, not a clinical call.

PI4KB p.Val66Met

c.196G>A · VCV4567782

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.0789 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 0.0011%, nfe)

Missense predictors

0/3 damaging

AlphaMissense, REVEL, SaProt

Computational evidence

Protein change
AlphaMissense	0.0789	likely benign
REVEL	0.011	strongly benign-leaning
SaProt	LLR -7.92	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 -1	GERP -5.2
Regional constraint	o/e 0.79	unconstrained · MANE · 8,680 bp · p 2.7e-05 · regional, not allelic
Overall
CADD	5.959	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 0.0011% European (non-Finnish) · 13/1,180,034 alleles

Filtering AF 0.000615% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.000474%

Overall 0.000867% 14/1,614,098 alleles · very rare

Ancestry group	Frequency	1 in
European (non-Finnish)grpmax	0.0011%	90,772
South Asian	0.0011%	91,086

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.Val66Met
Coding: c.196G>A
MANE Select: NM_001369623
Type: single nucleotide variant
Location: chr1:151316286 (GRCh38)
Gene constraint: LOEUF 0.421 · pLI 1.00 (gnomAD)
Structure: AlphaFold pLDDT 72.97 · 20 PDB
Residue 66: the pik helical domain; the 'interaction with acbd3' region

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

Similar variants

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
PI4KB p.Ala95Ser 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-val66met (accessed [today's date]).

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