Is APOBEC3B p.Phe296Ser (c.887T>C) pathogenic?

APOBEC3B p.Phe296Ser (c.887T>C) is classified Uncertain significance in APOBEC3B (ClinVar, Single submitter, 1 submitter; last evaluated 2020-07-27). AlphaMissense: likely pathogenic (0.9362); Very rare (popmax 0.000171%, nfe); Associated with APOBEC3B-related condition.

What condition is associated with APOBEC3B p.Phe296Ser (c.887T>C)?

APOBEC3B p.Phe296Ser (c.887T>C) is associated with APOBEC3B-related condition (ClinVar).

How common is APOBEC3B p.Phe296Ser (c.887T>C) in the general population?

APOBEC3B p.Phe296Ser (c.887T>C) is very rare (popmax 0.000171%, nfe) (gnomAD).

What do computational predictors say about APOBEC3B p.Phe296Ser (c.887T>C)?

AlphaMissense predicts likely pathogenic (score 0.9362) — an in-silico prediction, not a clinical call.

APOBEC3B p.Phe296Ser

c.887T>C · VCV3779923

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely pathogenic

0.9362 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 0.000171%, nfe)

Missense predictors

2/2 damaging

AlphaMissense, SaProt · REVEL no call

Conditions

APOBEC3B-related condition

Computational evidence

Protein change
AlphaMissense	0.9362	likely pathogenic · top 1% in APOBEC3B
REVEL	0.356	indeterminate
SaProt	LLR -15.50	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 5.8	GERP 1.5, phastCons 0.99
Regional constraint	o/e 0.24	constrained · MANE · 189 bp · p 3e-12 · regional, not allelic
Overall
CADD	20.7	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 0.000171% European (non-Finnish) · 2/1,172,606 alleles

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

Overall 0.000138% 2/1,445,232 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: APOBEC3B
Protein: p.Phe296Ser
Coding: c.887T>C
MANE Select: NM_004900
Type: single nucleotide variant
Location: chr22:38991495 (GRCh38)
Gene constraint: LOEUF 0.854 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 87.94 · 13 PDB
Residue 296: the cmp/dcmp-type deaminase 2 domain; an α-helix

Full APOBEC3B gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Disease context

APOBEC3B-related condition

Similar variants

APOBEC3B p.Arg351Cys Conflicting classifications of pathogenicity ★ ⚠ same condition
APOBEC3B p.Gln167Pro Uncertain significance ★ ⚠ same condition
APOBEC3B p.Asn23= Benign ★★ same type
APOBEC3B p.Pro206= Benign ★★ same type
APOBEC3B c.174+1G>T Uncertain significance ★ same type
APOBEC3B p.Ala242Ser Uncertain significance ★ ⚠ same type
APOBEC3B p.Ala331Ser Uncertain significance ★ ⚠ same type
APOBEC3B p.Ala375Val 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/apobec3b-p-phe296ser (accessed [today's date]).

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