Is APOOL p.Glu30Lys (c.88G>A) pathogenic?

APOOL p.Glu30Lys (c.88G>A) is classified Uncertain significance in APOOL (ClinVar, Single submitter, 1 submitter; last evaluated 2025-04-11). AlphaMissense: likely benign (0.0908); Ultra-rare (popmax 0.0508%, afr).

How common is APOOL p.Glu30Lys (c.88G>A) in the general population?

APOOL p.Glu30Lys (c.88G>A) is ultra-rare (popmax 0.0508%, afr) (gnomAD).

What do computational predictors say about APOOL p.Glu30Lys (c.88G>A)?

AlphaMissense predicts likely benign (score 0.0908) — an in-silico prediction, not a clinical call.

APOOL p.Glu30Lys

c.88G>A · VCV3935227

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.0908 · ACMG-weighted

gnomAD v4.1

Rare

ultra-rare (popmax 0.0508%, afr)

Missense predictors

0/3 damaging

AlphaMissense, REVEL, SaProt

Computational evidence

Protein change
AlphaMissense	0.0908	likely benign
REVEL	0.09	moderately benign-leaning
SaProt	LLR -7.58	tolerated
⇒ AlphaMissense, REVEL and SaProt all call this tolerated.
Splicing
SpliceAI	<0.2	all four deltas below 0.2 · G>T here scores Δ0.44 · evaluated, not missing
Constraint at this position
Conservation	phyloP 4.5	GERP 2, phastCons 1
Regional constraint	o/e 1.06	unconstrained · MANE · 84 kb · p 0.38 · regional, not allelic
Overall
CADD	20.8	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 0.0508% African / African-American · 29/57,089 alleles

Filtering AF 0.0363% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.0314%

Overall 0.00423% 51/1,206,985 alleles · ultra-rare exomes 33/1,095,539 · genomes 18/111,446 · joint denominator

Ancestry group	Frequency	1 in
African / African-Americangrpmax	0.0508%	1,969
Middle Eastern	0.023%	4,346
Remaining individualsnot grpmax-eligible	0.0126%	7,916
Admixed American	0.00441%	22,700
South Asian	0.00178%	56,251
European (non-Finnish)	0.00134%	74,468

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: APOOL
Protein: p.Glu30Lys
Coding: c.88G>A
MANE Select: NM_198450
Type: single nucleotide variant
Location: chrX:85046518 (GRCh38)
Structure: AlphaFold pLDDT 70.83

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

Similar variants

APOOL p.Ala124Glu Uncertain significance ★ ⚠ same type
APOOL p.Ala178Gly Uncertain significance ★ ⚠ same type
APOOL p.Ala241Ser Uncertain significance ★ ⚠ same type
APOOL p.Arg69Cys Uncertain significance ★ ⚠ same type
APOOL p.Arg69His Uncertain significance ★ ⚠ same type
APOOL p.Gln156His Uncertain significance ★ same type
APOOL p.Gln173His Uncertain significance ★ ⚠ same type
APOOL p.Glu56Ala 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/apool-p-glu30lys (accessed [today's date]).

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