Is PIK3C2B p.Arg306Gln (c.917G>A) pathogenic?

PIK3C2B p.Arg306Gln (c.917G>A) is classified Uncertain significance in PIK3C2B (ClinVar, Single submitter, 1 submitter; last evaluated 2025-01-24). AlphaMissense: likely benign (0.128); Very rare (popmax 0.00224%, eas).

How common is PIK3C2B p.Arg306Gln (c.917G>A) in the general population?

PIK3C2B p.Arg306Gln (c.917G>A) is very rare (popmax 0.00224%, eas) (gnomAD).

What do computational predictors say about PIK3C2B p.Arg306Gln (c.917G>A)?

AlphaMissense predicts likely benign (score 0.128) — an in-silico prediction, not a clinical call.

PIK3C2B p.Arg306Gln

c.917G>A · VCV3888900

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.128 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 0.00224%, eas)

Missense predictors

0/3 damaging

AlphaMissense, REVEL, SaProt

Computational evidence

Protein change
AlphaMissense	0.128	likely benign
REVEL	0.075	moderately benign-leaning
SaProt	LLR -6.68	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 4.1	GERP 1.4, phastCons 1
Regional constraint	o/e 0.97	unconstrained · MANE · 4,520 bp · p 0.49 · regional, not allelic
Overall
CADD	24.0	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 0.00224% East Asian · 1/44,646 alleles

Filtering AF 0.000888% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.000726%

Overall 0.00126% 20/1,587,890 alleles · very rare exomes 19/1,435,670 · genomes 1/152,220 · joint denominator

Ancestry group	Frequency	1 in
East Asiangrpmax	0.00224%	44,646
European (non-Finnish)	0.00146%	68,597
African / African-American	0.00135%	74,112
South Asian	0.00115%	86,742

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: PIK3C2B
Protein: p.Arg306Gln
Coding: c.917G>A
MANE Select: NM_001377334
Type: single nucleotide variant
Location: chr1:204468886 (GRCh38)
Gene constraint: LOEUF 0.557 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 75.07
Residue 306: the 'disordered' region

Full PIK3C2B gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Similar variants

PIK3C2B c.1034+7G>A Benign/Likely benign ★★ same type
PIK3C2B p.Asn1245= Benign ★★ same type
PIK3C2B p.Asn52= Benign ★★ same type
PIK3C2B p.Pro273His Benign/Likely benign ★★ ⚠ same type
PIK3C2B p.Ser1364Cys Benign ★★ same type
PIK3C2B p.Tyr1189= Likely benign ★★ same type
PIK3C2B p.Val1602Ile Benign ★★ same type
PIK3C2B p.Ala246Val 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/pik3c2b-p-arg306gln (accessed [today's date]).

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