Is APOOL p.Gln156His (c.468G>C) pathogenic?

APOOL p.Gln156His (c.468G>C) is classified Uncertain significance in APOOL (ClinVar, Single submitter, 1 submitter; last evaluated 2025-12-24). AlphaMissense: ambiguous (0.5271); Ultra-rare (popmax 0.0108%, afr).

How common is APOOL p.Gln156His (c.468G>C) in the general population?

APOOL p.Gln156His (c.468G>C) is ultra-rare (popmax 0.0108%, afr) (gnomAD).

What do computational predictors say about APOOL p.Gln156His (c.468G>C)?

AlphaMissense predicts ambiguous (score 0.5271) — an in-silico prediction, not a clinical call.

APOOL p.Gln156His

c.468G>C · VCV4831388

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

ambiguous

0.5271 · ACMG-weighted

gnomAD v4.1

Rare

ultra-rare (popmax 0.0108%, afr)

Computational evidence

Protein change
AlphaMissense	0.5271	ambiguous
REVEL	0.596	indeterminate
SaProt	LLR -10.53	damaging
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 1.7	GERP 2, phastCons 1
Regional constraint	o/e 1.06	unconstrained · MANE · 84 kb · p 0.38 · regional, not allelic
Overall
CADD	21.4	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

Grpmax group 0.0108% African / African-American · 6/55,464 alleles

Filtering AF 0.00468% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.00314%

Overall 0.000611% 7/1,144,751 alleles · ultra-rare

Ancestry group	Frequency	1 in
African / African-Americangrpmax	0.0108%	9,244
European (non-Finnish)	0.000117%	857,067

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.Gln156His
Coding: c.468G>C
MANE Select: NM_198450
Type: single nucleotide variant
Location: chrX:85067200 (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.Gln173His Uncertain significance ★ ⚠ same type
APOOL p.Glu30Lys 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-gln156his (accessed [today's date]).

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