Is PI4KA p.Pro325Ser (c.973C>T) pathogenic?

PI4KA p.Pro325Ser (c.973C>T) is classified Uncertain significance in PI4KA (ClinVar, Single submitter, 1 submitter; last evaluated 2023-01-03). AlphaMissense: likely benign (0.1053); Very rare (popmax 0.00267%, afr).

How common is PI4KA p.Pro325Ser (c.973C>T) in the general population?

PI4KA p.Pro325Ser (c.973C>T) is very rare (popmax 0.00267%, afr) (gnomAD).

What do computational predictors say about PI4KA p.Pro325Ser (c.973C>T)?

AlphaMissense predicts likely benign (score 0.1053) — an in-silico prediction, not a clinical call.

PI4KA p.Pro325Ser

c.973C>T · rs1242346793 · VCV2507308

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.1053 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 0.00267%, afr)

Missense predictors

0/3 damaging

AlphaMissense, REVEL, SaProt

Computational evidence

Protein change
AlphaMissense	0.1053	likely benign
REVEL	0.165	moderately benign-leaning
SaProt	LLR -6.27	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 12	phastCons 1
Regional constraint	o/e 0.97	unconstrained · MANE · 54 kb · p 0.51 · regional, not allelic
Overall
CADD	21.7	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 0.00267% African / African-American · 2/74,898 alleles

Filtering AF 0.000443% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.000166%

Overall 0.000124% 2/1,613,506 alleles · very rare

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: PI4KA
Protein: p.Pro325Ser
Coding: c.973C>T
MANE Select: NM_058004
dbSNP: rs1242346793
Type: single nucleotide variant
Location: chr22:20813390 (GRCh38)
Gene constraint: LOEUF 0.548 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 80.42 · 4 PDB

Full PI4KA gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Similar variants

SERPIND1 p.Met325Val Uncertain significance ★ ⚠ same residue
PI4KA p.Arg618Ter Likely pathogenic ★★ same type
PI4KA p.Asp1854Asn Pathogenic/Likely pathogenic ★★ same type
PI4KA p.Glu1152Lys Likely pathogenic ★★ same type
PI4KA p.Pro1992Ser Likely pathogenic ★★ ⚠ same type
PI4KA p.Ala1037Thr Uncertain significance ★★ ⚠ same type
PI4KA p.Ala940Val Uncertain significance ★★ ⚠ same type
PI4KA p.Asp1713His 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/pi4ka-p-pro325ser (accessed [today's date]).

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