Is PI4KB p.Ser604Ala (c.1810T>G) pathogenic?

PI4KB p.Ser604Ala (c.1810T>G) is classified Uncertain significance in PI4KB (ClinVar, Single submitter, 1 submitter; last evaluated 2024-02-06). AlphaMissense: ambiguous (0.4634); Absent from gnomAD v4.1.

How common is PI4KB p.Ser604Ala (c.1810T>G) in the general population?

PI4KB p.Ser604Ala (c.1810T>G) is absent from gnomAD v4.1 (gnomAD).

What do computational predictors say about PI4KB p.Ser604Ala (c.1810T>G)?

AlphaMissense predicts ambiguous (score 0.4634) — an in-silico prediction, not a clinical call.

PI4KB p.Ser604Ala

c.1810T>G · rs2528670109 · VCV3212539

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

ambiguous

0.4634 · ACMG-weighted

gnomAD v4.1

Absent

absent from gnomAD v4.1

Missense predictors

1/2 damaging

REVEL, SaProt · AlphaMissense no call

Computational evidence

Protein change
AlphaMissense	0.4634	ambiguous
REVEL	0.693	pathogenic-leaning
SaProt	LLR -6.95	tolerated
⇒ REVEL calls this damaging; SaProt does not; AlphaMissense makes no call.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 11	GERP 2.5, phastCons 1
Regional constraint	o/e 0.57	unconstrained · MANE · 8,940 bp · p 6.9e-19 · regional, not allelic
Overall
CADD	31.0	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

Absent from gnomAD v4.1. Not observed in any sequenced alleles — a rarity signal (ACMG PM2-supporting), not evidence of pathogenicity on its own.

Variant & gene context

Gene: PI4KB
Protein: p.Ser604Ala
Coding: c.1810T>G
MANE Select: NM_001369623
dbSNP: rs2528670109
Type: single nucleotide variant
Location: chr1:151299013 (GRCh38)
Gene constraint: LOEUF 0.421 · pLI 1.00 (gnomAD)
Structure: AlphaFold pLDDT 72.97 · 20 PDB
Residue 604: the pi3k/pi4k catalytic domain; a β-strand

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-ser604ala (accessed [today's date]).

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