Is PI4KA p.Pro2012= (c.6036C>T) pathogenic?

PI4KA p.Pro2012= (c.6036C>T) is classified Benign/Likely benign in PI4KA (ClinVar, Multiple submitters, 3 submitters; last evaluated 2026-04-01). Rare (popmax 0.263%, nfe).

How common is PI4KA p.Pro2012= (c.6036C>T) in the general population?

PI4KA p.Pro2012= (c.6036C>T) is rare (popmax 0.263%, nfe) (gnomAD).

PI4KA p.Pro2012=

c.6036C>T · rs150339960 · VCV784557

Benign/Likely benign Multiple submitters

Classification

Benign/Likely benign

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 3 submitters

gnomAD v4.1

Rare

rare (popmax 0.263%, nfe)

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 0.9	phastCons 1
Overall
CADD	9.546	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.263% European (non-Finnish) · 3,088/1,172,862 alleles

Filtering AF 0.255% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.252%

Overall 0.212% 3,411/1,605,924 alleles · rare exomes 3,307/1,454,324 · genomes 104/151,600 · joint denominator

Ancestry group	Frequency	1 in
Amishnot grpmax-eligible	0.443%	225
European (non-Finnish)grpmax	0.263%	380
Remaining individualsnot grpmax-eligible	0.167%	598
South Asian	0.0925%	1,081
Ashkenazi Jewishnot grpmax-eligible	0.0677%	1,476
Finnishnot grpmax-eligible	0.0626%	1,596
Admixed American	0.0618%	1,618
Middle Eastern	0.0496%	2,017
African / African-American	0.04%	2,499
East Asian	0.00223%	44,880

Amish shows a higher raw frequency than the grpmax group above it. gnomAD excludes bottlenecked groups — Finnish, Ashkenazi Jewish, Amish and “Remaining individuals” — from grpmax, because founder effects make their frequencies unrepresentative for filtering. The table is sorted by frequency, so an excluded group can sit above the grpmax row.

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.Pro2012=
Coding: c.6036C>T
MANE Select: NM_058004
dbSNP: rs150339960
Type: single nucleotide variant
Location: chr22:20710746 (GRCh38)
Gene constraint: LOEUF 0.548 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 80.42 · 4 PDB
Residue 2012: an α-helix; the pi3k/pi4k catalytic domain; a UniProt-annotated variant site (in nedsplb)

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

Similar variants

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
PI4KA p.Asp1866Asn 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-pro2012 (accessed [today's date]).

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