Is APOBEC1 p.Pro191Arg (c.572C>G) pathogenic?

APOBEC1 p.Pro191Arg (c.572C>G) is classified Uncertain significance in APOBEC1 (ClinVar, Single submitter, 1 submitter; last evaluated 2025-06-06). AlphaMissense: ambiguous (0.3637); Very rare (popmax 0.00134%, afr).

How common is APOBEC1 p.Pro191Arg (c.572C>G) in the general population?

APOBEC1 p.Pro191Arg (c.572C>G) is very rare (popmax 0.00134%, afr) (gnomAD).

What do computational predictors say about APOBEC1 p.Pro191Arg (c.572C>G)?

AlphaMissense predicts ambiguous (score 0.3637) — an in-silico prediction, not a clinical call.

APOBEC1 p.Pro191Arg

c.572C>G · VCV3933971

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

ambiguous

0.3637 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 0.00134%, afr)

Computational evidence

Protein change
AlphaMissense	0.3637	ambiguous
REVEL	0.534	indeterminate
SaProt	LLR -8.78	tolerated
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 7.8	GERP 1.7, phastCons 1
Regional constraint	o/e 0.88	unconstrained · MANE · 16 kb · p 0.034 · regional, not allelic
Overall
CADD	23.3	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 0.00134% African / African-American · 1/74,758 alleles

Overall 0.000658% 1/151,988 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: APOBEC1
Protein: p.Pro191Arg
Coding: c.572C>G
MANE Select: NM_001644
Type: single nucleotide variant
Location: chr12:7649686 (GRCh38)
Gene constraint: LOEUF 1.086 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 88.16 · 1 PDB

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-pro191arg (accessed [today's date]).

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