Is APOOL p.Pro195Arg (c.584C>G) pathogenic?

APOOL p.Pro195Arg (c.584C>G) is classified Likely benign in APOOL (ClinVar, Single submitter, 1 submitter; last evaluated 2022-09-01). AlphaMissense: likely benign (0.0767); Rare (popmax 0.274%, afr).

How common is APOOL p.Pro195Arg (c.584C>G) in the general population?

APOOL p.Pro195Arg (c.584C>G) is rare (popmax 0.274%, afr) (gnomAD).

What do computational predictors say about APOOL p.Pro195Arg (c.584C>G)?

AlphaMissense predicts likely benign (score 0.0767) — an in-silico prediction, not a clinical call.

APOOL p.Pro195Arg

c.584C>G · rs201017526 · VCV2660999

Likely benign Single submitter

Classification

Likely benign

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.0767 · ACMG-weighted

gnomAD v4.1

Rare

rare (popmax 0.274%, afr)

Missense predictors

0/3 damaging

AlphaMissense, REVEL, SaProt

Computational evidence

Protein change
AlphaMissense	0.0767	likely benign
REVEL	0.049	moderately benign-leaning
SaProt	LLR -7.82	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 0.062	GERP 1.2, phastCons 0.001
Regional constraint	o/e 1.06	unconstrained · MANE · 84 kb · p 0.38 · regional, not allelic
Overall
CADD	1.303	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 0.274% African / African-American · 152/55,485 alleles

Filtering AF 0.238% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.225%

Overall 0.0137% 159/1,162,364 alleles · rare

Ancestry group	Frequency	1 in
African / African-Americangrpmax	0.274%	365
Remaining individualsnot grpmax-eligible	0.0131%	7,639
Admixed American	0.00266%	37,622

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.Pro195Arg
Coding: c.584C>G
MANE Select: NM_198450
dbSNP: rs201017526
Type: single nucleotide variant
Location: chrX:85074095 (GRCh38)
Structure: AlphaFold pLDDT 70.83
Residue 195: 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-pro195arg (accessed [today's date]).

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