Is APOOL p.Leu147Ser (c.440T>C) pathogenic?

APOOL p.Leu147Ser (c.440T>C) is classified Uncertain significance in APOOL (ClinVar, Single submitter, 1 submitter; last evaluated 2022-05-18). AlphaMissense: ambiguous (0.5572); Very rare (popmax 0.00359%, afr).

How common is APOOL p.Leu147Ser (c.440T>C) in the general population?

APOOL p.Leu147Ser (c.440T>C) is very rare (popmax 0.00359%, afr) (gnomAD).

What do computational predictors say about APOOL p.Leu147Ser (c.440T>C)?

AlphaMissense predicts ambiguous (score 0.5572) — an in-silico prediction, not a clinical call.

APOOL p.Leu147Ser

c.440T>C · rs960559839 · VCV2290309

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

ambiguous

0.5572 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 0.00359%, afr)

Computational evidence

Protein change
AlphaMissense	0.5572	ambiguous
REVEL	0.302	indeterminate
SaProt	LLR -13.47	damaging
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 5.9	GERP 3.7, phastCons 1
Regional constraint	o/e 1.06	unconstrained · MANE · 84 kb · p 0.38 · regional, not allelic
Overall
CADD	25.2	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 0.00359% African / African-American · 2/55,684 alleles

Filtering AF 0.000596% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.000223%

Overall 0.000345% 4/1,160,150 alleles · very rare

Ancestry group	Frequency	1 in
African / African-Americangrpmax	0.00359%	27,842
Remaining individualsnot grpmax-eligible	0.00219%	45,592
European (non-Finnish)	0.000115%	868,614

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.Leu147Ser
Coding: c.440T>C
MANE Select: NM_198450
dbSNP: rs960559839
Type: single nucleotide variant
Location: chrX:85067172 (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.Glu30Lys 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-leu147ser (accessed [today's date]).

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