Is APOBEC1 p.Arg48Trp (c.142C>T) pathogenic?

APOBEC1 p.Arg48Trp (c.142C>T) is classified Uncertain significance in APOBEC1 (ClinVar, Single submitter, 1 submitter; last evaluated 2024-02-21). AlphaMissense: likely benign (0.0911); Very rare (popmax 0.00333%, amr).

How common is APOBEC1 p.Arg48Trp (c.142C>T) in the general population?

APOBEC1 p.Arg48Trp (c.142C>T) is very rare (popmax 0.00333%, amr) (gnomAD).

What do computational predictors say about APOBEC1 p.Arg48Trp (c.142C>T)?

AlphaMissense predicts likely benign (score 0.0911) — an in-silico prediction, not a clinical call.

APOBEC1 p.Arg48Trp

c.142C>T · rs756281691 · VCV3127931

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.0911 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 0.00333%, amr)

Missense predictors

0/3 damaging

AlphaMissense, REVEL, SaProt

Computational evidence

Protein change
AlphaMissense	0.0911	likely benign
REVEL	0.127	moderately benign-leaning
SaProt	LLR -8.52	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 0.47	GERP -3.1, phastCons 0.008
Regional constraint	o/e 0.88	unconstrained · MANE · 16 kb · p 0.034 · regional, not allelic
Overall
CADD	16.36	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 0.00333% Admixed American · 2/59,978 alleles

Filtering AF 0.00103% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.00083%

Overall 0.00149% 24/1,613,838 alleles · very rare

Ancestry group	Frequency	1 in
Admixed Americangrpmax	0.00333%	29,989
East Asian	0.00223%	44,888
European (non-Finnish)	0.00161%	62,106
Remaining individualsnot grpmax-eligible	0.0016%	62,482
African / African-American	0.00134%	74,854

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.Arg48Trp
Coding: c.142C>T
MANE Select: NM_001644
dbSNP: rs756281691
Type: single nucleotide variant
Location: chr12:7652738 (GRCh38)
Gene constraint: LOEUF 1.086 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 88.16 · 1 PDB
Residue 48: 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.Asn136Tyr Uncertain significance ★ ⚠ same type
APOBEC1 p.Asn158Asp Uncertain significance ★ ⚠ same type
APOBEC1 p.Asp75Gly Uncertain significance ★ ⚠ same type
APOBEC1 p.Cys37Arg 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-arg48trp (accessed [today's date]).

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