Is APOOL p.Ser265Asn (c.794G>A) pathogenic?

APOOL p.Ser265Asn (c.794G>A) is classified Uncertain significance in APOOL (ClinVar, Single submitter, 1 submitter; last evaluated 2025-10-24). AlphaMissense: likely pathogenic (0.6409); Very rare (popmax 0.000113%, nfe).

How common is APOOL p.Ser265Asn (c.794G>A) in the general population?

APOOL p.Ser265Asn (c.794G>A) is very rare (popmax 0.000113%, nfe) (gnomAD).

What do computational predictors say about APOOL p.Ser265Asn (c.794G>A)?

AlphaMissense predicts likely pathogenic (score 0.6409) — an in-silico prediction, not a clinical call.

APOOL p.Ser265Asn

c.794G>A · VCV4641807

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely pathogenic

0.6409 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 0.000113%, nfe)

Missense predictors

1/3 damaging

AlphaMissense, REVEL, SaProt

Computational evidence

Protein change
AlphaMissense	0.6409	likely pathogenic · top 9% in APOOL
REVEL	0.14	moderately benign-leaning
SaProt	LLR -7.21	tolerated
⇒ AlphaMissense calls this damaging; REVEL and SaProt do not.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 8.4	GERP 3.5, phastCons 1
Regional constraint	o/e 1.06	unconstrained · MANE · 84 kb · p 0.38 · regional, not allelic
Overall
CADD	24.2	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 0.000113% European (non-Finnish) · 1/883,374 alleles

Overall 9.3e-05% 1/1,074,825 alleles · very rare

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.Ser265Asn
Coding: c.794G>A
MANE Select: NM_198450
Type: single nucleotide variant
Location: chrX:85087665 (GRCh38)
Structure: AlphaFold pLDDT 70.83
Residue 265: the 'disordered' region

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-ser265asn (accessed [today's date]).

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