Is APOBEC3B p.Thr95Ala (c.283A>G) pathogenic?

APOBEC3B p.Thr95Ala (c.283A>G) is classified Uncertain significance in APOBEC3B (ClinVar, Single submitter, 1 submitter; last evaluated 2025-02-22). AlphaMissense: likely benign (0.3233); Very rare (popmax 0.00558%, sas).

How common is APOBEC3B p.Thr95Ala (c.283A>G) in the general population?

APOBEC3B p.Thr95Ala (c.283A>G) is very rare (popmax 0.00558%, sas) (gnomAD).

What do computational predictors say about APOBEC3B p.Thr95Ala (c.283A>G)?

AlphaMissense predicts likely benign (score 0.3233) — an in-silico prediction, not a clinical call.

APOBEC3B p.Thr95Ala

c.283A>G · VCV3885933

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.3233 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 0.00558%, sas)

Missense predictors

0/3 damaging

AlphaMissense, REVEL, SaProt

Computational evidence

Protein change
AlphaMissense	0.3233	likely benign
REVEL	0.113	moderately benign-leaning
SaProt	LLR -8.91	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 4.9	GERP 0.68, phastCons 1
Regional constraint	o/e 0.39	unconstrained · MANE · 127 bp · p 1.5e-05 · regional, not allelic
Overall
CADD	16.74	PHRED · no single calibrated threshold — expert panels disagree

ClinVar classifies this uncertain; the computational predictors unanimously lean tolerated — 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 0.00558% South Asian · 5/89,592 alleles

Filtering AF 0.00213% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.00138%

Overall 0.00055% 8/1,453,668 alleles · very rare

Ancestry group	Frequency	1 in
South Asiangrpmax	0.00558%	17,918
Remaining individualsnot grpmax-eligible	0.00323%	30,937
European (non-Finnish)	8.5e-05%	1,176,340

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.Thr95Ala
Coding: c.283A>G
MANE Select: NM_004900
Type: single nucleotide variant
Location: chr22:38985920 (GRCh38)
Gene constraint: LOEUF 0.854 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 87.94 · 13 PDB
Residue 95: the cmp/dcmp-type deaminase 1 domain; an α-helix

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.Ala331Ser 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

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-thr95ala (accessed [today's date]).

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