Is APOBEC1 p.Ser89Cys (c.266C>G) pathogenic?

APOBEC1 p.Ser89Cys (c.266C>G) is classified Uncertain significance in APOBEC1 (ClinVar, Single submitter, 1 submitter; last evaluated 2023-03-01). AlphaMissense: likely pathogenic (0.704); Very rare (popmax 0.00136%, nfe).

How common is APOBEC1 p.Ser89Cys (c.266C>G) in the general population?

APOBEC1 p.Ser89Cys (c.266C>G) is very rare (popmax 0.00136%, nfe) (gnomAD).

What do computational predictors say about APOBEC1 p.Ser89Cys (c.266C>G)?

AlphaMissense predicts likely pathogenic (score 0.704) — an in-silico prediction, not a clinical call.

APOBEC1 p.Ser89Cys

c.266C>G · rs147151417 · VCV2472524

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely pathogenic

0.704 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 0.00136%, nfe)

Missense predictors

2/2 damaging

AlphaMissense, SaProt · REVEL no call

Computational evidence

Protein change
AlphaMissense	0.704	likely pathogenic
REVEL	0.595	indeterminate
SaProt	LLR -10.54	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 9.2	GERP 1.7, phastCons 1
Regional constraint	o/e 0.88	unconstrained · MANE · 16 kb · p 0.034 · regional, not allelic
Overall
CADD	27.3	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 0.00136% European (non-Finnish) · 16/1,180,024 alleles

Filtering AF 0.000803% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.00065%

Overall 0.00116% 17/1,461,876 alleles · very rare

Ancestry group	Frequency	1 in
European (non-Finnish)grpmax	0.00136%	73,752
African / African-American	0.00133%	75,066

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: APOBEC1
Protein: p.Ser89Cys
Coding: c.266C>G
MANE Select: NM_001644
dbSNP: rs147151417
Type: single nucleotide variant
Location: chr12:7652614 (GRCh38)
Gene constraint: LOEUF 1.086 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 88.16 · 1 PDB
Residue 89: the cmp/dcmp-type deaminase domain

Full APOBEC1 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Similar variants

APOBEC1 p.Ala146Gly Uncertain significance ★ ⚠ same type
APOBEC1 p.Ala179Thr Uncertain significance ★ ⚠ same type
APOBEC1 p.Arg15Gly Uncertain significance ★ ⚠ same type
APOBEC1 p.Arg236Lys Uncertain significance ★ ⚠ same type
APOBEC1 p.Arg48Trp Uncertain significance ★ ⚠ same type
APOBEC1 p.Asn136Tyr Uncertain significance ★ ⚠ same type
APOBEC1 p.Asn158Asp Uncertain significance ★ ⚠ same type
APOBEC1 p.Asp75Gly 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/apobec1-p-ser89cys (accessed [today's date]).

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