Is APOL3 p.Gln34Pro (c.101A>C) pathogenic?

APOL3 p.Gln34Pro (c.101A>C) is classified Uncertain significance in APOL3 (ClinVar, Single submitter, 1 submitter; last evaluated 2022-08-29). AlphaMissense: likely benign (0.0802); Very rare (popmax 0.000169%, nfe).

How common is APOL3 p.Gln34Pro (c.101A>C) in the general population?

APOL3 p.Gln34Pro (c.101A>C) is very rare (popmax 0.000169%, nfe) (gnomAD).

What do computational predictors say about APOL3 p.Gln34Pro (c.101A>C)?

AlphaMissense predicts likely benign (score 0.0802) — an in-silico prediction, not a clinical call.

APOL3 p.Gln34Pro

c.101A>C · rs1237150510 · VCV2309299

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.0802 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 0.000169%, nfe)

Missense predictors

0/3 damaging

AlphaMissense, REVEL, SaProt

Computational evidence

Protein change
AlphaMissense	0.0802	likely benign
REVEL	0.098	moderately benign-leaning
SaProt	LLR -4.98	tolerated
⇒ AlphaMissense, REVEL and SaProt all call this tolerated.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Pangolin	Δ0.58	gain · loss 0.00 · not in the SpliceAI release · independent
Constraint at this position
Conservation	phyloP -20
Overall
CADD	0.021	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 0.000169% European (non-Finnish) · 2/1,179,950 alleles

Filtering AF 2.8e-05% ClinGen BA1/BS1 input FAF95, joint · FAF99 1.1e-05%

Overall 0.000137% 2/1,461,848 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: APOL3
Protein: p.Gln34Pro
Coding: c.101A>C
MANE Select: NM_145639 · reported on NM_145640
dbSNP: rs1237150510
Type: single nucleotide variant
Location: chr22:36160791 (GRCh38)
Gene constraint: LOEUF 1.748 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 60.87

Full APOL3 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Similar variants

APOL3 c.-100A>G Benign ★★ same type
APOL3 p.Ala157Thr Benign ★★ same type
APOL3 p.Ala64Val Benign ★★ same type
APOL3 p.Asn31Asp Benign ★★ same type
APOL3 p.Cys13Trp Likely benign ★★ same type
APOL3 p.Cys22= Benign ★★ same type
APOL3 p.Gly35Val Likely benign ★★ same type
APOL3 p.Thr149Ile Benign ★★ ⚠ 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/apol3-p-gln34pro (accessed [today's date]).

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