Is APOBEC3B p.Ala331Ser (c.991G>T) pathogenic?

APOBEC3B p.Ala331Ser (c.991G>T) is classified Uncertain significance in APOBEC3B (ClinVar, Single submitter, 1 submitter; last evaluated 2025-08-29). AlphaMissense: likely benign (0.2365); Very rare (popmax 0.00146%, afr).

How common is APOBEC3B p.Ala331Ser (c.991G>T) in the general population?

APOBEC3B p.Ala331Ser (c.991G>T) is very rare (popmax 0.00146%, afr) (gnomAD).

What do computational predictors say about APOBEC3B p.Ala331Ser (c.991G>T)?

AlphaMissense predicts likely benign (score 0.2365) — an in-silico prediction, not a clinical call.

APOBEC3B p.Ala331Ser

c.991G>T · VCV4126191

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.2365 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 0.00146%, afr)

Missense predictors

1/3 damaging

AlphaMissense, REVEL, SaProt

Computational evidence

Protein change
AlphaMissense	0.2365	likely benign
REVEL	0.177	moderately benign-leaning
SaProt	LLR -10.26	damaging
⇒ SaProt calls this damaging; AlphaMissense and REVEL do not.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP -0.14	GERP -2
Regional constraint	o/e 0.75	unconstrained · MANE · 920 bp · p 0.011 · regional, not allelic
Overall
CADD	19.01	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 0.00146% African / African-American · 1/68,668 alleles

Overall 7.45e-05% 1/1,341,754 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.Ala331Ser
Coding: c.991G>T
MANE Select: NM_004900
Type: single nucleotide variant
Location: chr22:38991599 (GRCh38)
Gene constraint: LOEUF 0.854 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 87.94 · 13 PDB

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

Similar variants

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.Ala375Val Uncertain significance ★ ⚠ same type
APOBEC3B p.Arg183Cys Uncertain significance ★ ⚠ same type
APOBEC3B p.Arg212Leu Uncertain significance ★ ⚠ same type
APOBEC3B p.Arg274Gly 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-ala331ser (accessed [today's date]).

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