Is APOBEC2 p.Pro109Arg (c.326C>G) pathogenic?

APOBEC2 p.Pro109Arg (c.326C>G) is classified Uncertain significance in APOBEC2 (ClinVar, Single submitter, 1 submitter; last evaluated 2025-02-07). AlphaMissense: ambiguous (0.408); Absent from gnomAD v4.1.

How common is APOBEC2 p.Pro109Arg (c.326C>G) in the general population?

APOBEC2 p.Pro109Arg (c.326C>G) is absent from gnomAD v4.1 (gnomAD).

What do computational predictors say about APOBEC2 p.Pro109Arg (c.326C>G)?

AlphaMissense predicts ambiguous (score 0.408) — an in-silico prediction, not a clinical call.

APOBEC2 p.Pro109Arg

c.326C>G · VCV3885891

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

ambiguous

0.408 · ACMG-weighted

gnomAD v4.1

Absent

absent from gnomAD v4.1

Computational evidence

Protein change
AlphaMissense	0.408	ambiguous
REVEL	0.313	indeterminate
SaProt	LLR -7.71	tolerated
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 7.6	GERP 2.2, phastCons 1
Regional constraint	o/e 1.10	unconstrained · MANE · 8,520 bp · p 0.1 · regional, not allelic
Overall
CADD	25.0	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

Absent from gnomAD v4.1. Not observed in any sequenced alleles — a rarity signal (ACMG PM2-supporting), not evidence of pathogenicity on its own.

Variant & gene context

Gene: APOBEC2
Protein: p.Pro109Arg
Coding: c.326C>G
MANE Select: NM_006789
Type: single nucleotide variant
Location: chr6:41061522 (GRCh38)
Gene constraint: LOEUF 1.085 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 73.10 · 1 PDB
Residue 109: the cmp/dcmp-type deaminase domain

Full APOBEC2 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Similar variants

APOBEC2 p.Ala2Asp Uncertain significance ★ ⚠ same type
APOBEC2 p.Ala8Val Uncertain significance ★ ⚠ same type
APOBEC2 p.Ala95Val Uncertain significance ★ ⚠ same type
APOBEC2 p.Arg116Trp Uncertain significance ★ ⚠ same type
APOBEC2 p.Arg46Gln Uncertain significance ★ ⚠ same type
APOBEC2 p.Arg46Trp Uncertain significance ★ ⚠ same type
APOBEC2 p.Arg57Trp Uncertain significance ★ ⚠ same type
APOBEC2 p.Arg87Trp 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/apobec2-p-pro109arg (accessed [today's date]).

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