Is APOBEC2 p.Ile208Val (c.622A>G) pathogenic?

APOBEC2 p.Ile208Val (c.622A>G) is classified Likely benign in APOBEC2 (ClinVar, Single submitter, 1 submitter; last evaluated 2022-12-06). AlphaMissense: likely benign (0.1458); Very rare (popmax 0.00167%, amr).

How common is APOBEC2 p.Ile208Val (c.622A>G) in the general population?

APOBEC2 p.Ile208Val (c.622A>G) is very rare (popmax 0.00167%, amr) (gnomAD).

What do computational predictors say about APOBEC2 p.Ile208Val (c.622A>G)?

AlphaMissense predicts likely benign (score 0.1458) — an in-silico prediction, not a clinical call.

APOBEC2 p.Ile208Val

c.622A>G · rs2532530944 · VCV2333148

Likely benign Single submitter

Classification

Likely benign

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.1458 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 0.00167%, amr)

Missense predictors

0/3 damaging

AlphaMissense, REVEL, SaProt

Computational evidence

Protein change
AlphaMissense	0.1458	likely benign
REVEL	0.121	moderately benign-leaning
SaProt	LLR -6.77	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 4	GERP -1.1, phastCons 1
Regional constraint	o/e 1.10	unconstrained · MANE · 8,520 bp · p 0.1 · regional, not allelic
Overall
CADD	19.29	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 0.00167% Admixed American · 1/60,026 alleles

Overall 6.84e-05% 1/1,461,878 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: APOBEC2
Protein: p.Ile208Val
Coding: c.622A>G
MANE Select: NM_006789
dbSNP: rs2532530944
Type: single nucleotide variant
Location: chr6:41061818 (GRCh38)
Gene constraint: LOEUF 1.085 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 73.10 · 1 PDB
Residue 208: an α-helix

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-ile208val (accessed [today's date]).

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