Is PI4KB p.Ala106= (c.318C>T) pathogenic?

PI4KB p.Ala106= (c.318C>T) is classified Likely benign in PI4KB (ClinVar, Single submitter, 1 submitter; last evaluated 2025-07-01). Ultra-rare (popmax 0.0187%, sas).

How common is PI4KB p.Ala106= (c.318C>T) in the general population?

PI4KB p.Ala106= (c.318C>T) is ultra-rare (popmax 0.0187%, sas) (gnomAD).

PI4KB p.Ala106=

c.318C>T · VCV4084507

Likely benign Single submitter

Classification

Likely benign

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

gnomAD v4.1

Rare

ultra-rare (popmax 0.0187%, sas)

Computational evidence

Protein change
Missense predictors do not apply to this variant type; conservation carries the signal.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 0.92	GERP -1.8, phastCons 0.36
Overall
CADD	7.312	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.0187% South Asian · 17/91,068 alleles

Filtering AF 0.0118% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.00976%

Overall 0.00198% 32/1,613,876 alleles · ultra-rare

Ancestry group	Frequency	1 in
South Asiangrpmax	0.0187%	5,357
Remaining individualsnot grpmax-eligible	0.0016%	62,494
European (non-Finnish)	0.00119%	84,276

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.Ala106=
Coding: c.318C>T
MANE Select: NM_001369623
Type: single nucleotide variant
Location: chr1:151316164 (GRCh38)
Gene constraint: LOEUF 0.421 · pLI 1.00 (gnomAD)
Structure: AlphaFold pLDDT 72.97 · 20 PDB
Residue 106: the pik helical domain; the 'disordered' region

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

Similar variants

PI4KB p.Ala106Val Uncertain significance ★ ⚠ 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.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-ala106 (accessed [today's date]).

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