Is APOBEC2 p.Arg46Trp (c.136C>T) pathogenic?

APOBEC2 p.Arg46Trp (c.136C>T) is classified Uncertain significance in APOBEC2 (ClinVar, Single submitter, 1 submitter; last evaluated 2025-08-31). AlphaMissense: likely pathogenic (0.6515); Very rare (popmax 0.00556%, afr).

How common is APOBEC2 p.Arg46Trp (c.136C>T) in the general population?

APOBEC2 p.Arg46Trp (c.136C>T) is very rare (popmax 0.00556%, afr) (gnomAD).

What do computational predictors say about APOBEC2 p.Arg46Trp (c.136C>T)?

AlphaMissense predicts likely pathogenic (score 0.6515) — an in-silico prediction, not a clinical call.

APOBEC2 p.Arg46Trp

c.136C>T · rs202202906 · VCV2390309

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely pathogenic

0.6515 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 0.00556%, afr)

Missense predictors

2/2 damaging

AlphaMissense, SaProt · REVEL no call

Computational evidence

Protein change
AlphaMissense	0.6515	likely pathogenic
REVEL	0.591	indeterminate
SaProt	LLR -11.19	damaging
⇒ AlphaMissense and SaProt both call this damaging; REVEL makes no call.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 1	GERP -2.4, phastCons 1
Regional constraint	o/e 1.10	unconstrained · MANE · 8,520 bp · p 0.1 · regional, not allelic
Overall
CADD	22.9	PHRED · no single calibrated threshold — expert panels disagree

ClinVar classifies this uncertain; the computational predictors unanimously lean damaging — 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 0.00556% African / African-American · 4/71,994 alleles

Filtering AF 0.00293% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.00261%

Overall 0.00347% 53/1,526,004 alleles · very rare

Ancestry group	Frequency	1 in
African / African-Americangrpmax	0.00556%	17,998
East Asian	0.00453%	22,067
European (non-Finnish)	0.00387%	25,861
Remaining individualsnot grpmax-eligible	0.00341%	29,303
Admixed American	0.00216%	46,334

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: APOBEC2
Protein: p.Arg46Trp
Coding: c.136C>T
MANE Select: NM_006789
dbSNP: rs202202906
Type: single nucleotide variant
Location: chr6:41061332 (GRCh38)
Gene constraint: LOEUF 1.085 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 73.10 · 1 PDB

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

Similar variants

APOBEC2 p.Arg46Gln Uncertain significance ★ ⚠ same residue
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.Arg57Trp Uncertain significance ★ ⚠ same type
APOBEC2 p.Arg87Trp Uncertain significance ★ ⚠ same type
APOBEC2 p.Asn17Lys 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-arg46trp (accessed [today's date]).

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