Is APOBEC3G p.Phe298Leu (c.894C>A) pathogenic?

APOBEC3G p.Phe298Leu (c.894C>A) is classified Uncertain significance in APOBEC3G (ClinVar, Single submitter, 1 submitter; last evaluated 2022-05-26). AlphaMissense: likely pathogenic (0.9515); Very rare (popmax 0.0011%, sas).

How common is APOBEC3G p.Phe298Leu (c.894C>A) in the general population?

APOBEC3G p.Phe298Leu (c.894C>A) is very rare (popmax 0.0011%, sas) (gnomAD).

What do computational predictors say about APOBEC3G p.Phe298Leu (c.894C>A)?

AlphaMissense predicts likely pathogenic (score 0.9515) — an in-silico prediction, not a clinical call.

APOBEC3G p.Phe298Leu

c.894C>A · rs746521588 · VCV2291317

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely pathogenic

0.9515 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 0.0011%, sas)

Missense predictors

2/3 damaging

AlphaMissense, REVEL, SaProt

Computational evidence

Protein change
AlphaMissense	0.9515	likely pathogenic · top 1% in APOBEC3G
REVEL	0.175	moderately benign-leaning
SaProt	LLR -11.02	damaging
⇒ AlphaMissense and SaProt call this damaging; REVEL does not.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP -2.5	GERP -0.53
Regional constraint	o/e 0.95	unconstrained · MANE · 10 kb · p 0.3 · regional, not allelic
Overall
CADD	15.64	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 0.0011% South Asian · 1/91,084 alleles

Filtering AF 6.8e-05% ClinGen BA1/BS1 input FAF95, joint · FAF99 1.9e-05%

Overall 0.000274% 4/1,461,888 alleles · very rare

Ancestry group	Frequency	1 in
South Asiangrpmax	0.0011%	91,084
European (non-Finnish)	0.000254%	393,343

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: APOBEC3G
Protein: p.Phe298Leu
Coding: c.894C>A
MANE Select: NM_021822
dbSNP: rs746521588
Type: single nucleotide variant
Location: chr22:39086437 (GRCh38)
Gene constraint: LOEUF 1.103 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 88.57 · 22 PDB
Residue 298: an α-helix; the cmp/dcmp-type deaminase 2 domain; the 'necessary for homooligomerization' region

Full APOBEC3G gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Similar variants

APOBEC3G p.Ala134Val Uncertain significance ★ ⚠ same type
APOBEC3G p.Ala312Val Uncertain significance ★ ⚠ same type
APOBEC3G p.Ala333Asp Uncertain significance ★ ⚠ same type
APOBEC3G p.Arg122Cys Uncertain significance ★ ⚠ same type
APOBEC3G p.Arg136Cys Uncertain significance ★ ⚠ same type
APOBEC3G p.Arg30Trp Uncertain significance ★ ⚠ same type
APOBEC3G p.Arg313His Uncertain significance ★ ⚠ same type
APOBEC3G p.Arg326Cys 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/apobec3g-p-phe298leu (accessed [today's date]).

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