Is APOBEC2 p.Ser199Pro (c.595T>C) pathogenic?

APOBEC2 p.Ser199Pro (c.595T>C) is classified Benign in APOBEC2 (ClinVar, Single submitter, 1 submitter; last evaluated 2018-07-31). AlphaMissense: likely benign (0.0623); Common (popmax 7.12%, afr) — too common for a highly-penetrant pathogenic allele.

What do computational predictors say about APOBEC2 p.Ser199Pro (c.595T>C)?

AlphaMissense predicts likely benign (score 0.0623) — an in-silico prediction, not a clinical call.

APOBEC2 p.Ser199Pro

Q: How common is APOBEC2 p.Ser199Pro (c.595T>C) in the general population?

APOBEC2 p.Ser199Pro (c.595T>C) is common (popmax 7.12%, afr) — too common for a highly-penetrant pathogenic allele (gnomAD).

c.595T>C · rs114127156 · VCV783754

Benign Single submitter

Classification

Benign

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.0623 · ACMG-weighted

gnomAD v4.1

Common

common (popmax 7.12%, afr) — too common for a highly-penetrant pathogenic allele

Missense predictors

0/3 damaging

AlphaMissense, REVEL, SaProt

Computational evidence

Protein change
AlphaMissense	0.0623	likely benign
REVEL	0.07	moderately benign-leaning
SaProt	LLR -5.74	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 0.48	GERP -2.5, phastCons 1
Regional constraint	o/e 1.10	unconstrained · MANE · 8,520 bp · p 0.1 · regional, not allelic
Overall
CADD	18.01	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 7.12% African / African-American · 5,342/75,020 alleles

Filtering AF 6.96% ClinGen BA1/BS1 input FAF95, joint · FAF99 6.9%

Overall 0.424% 6,845/1,614,136 alleles · common exomes 3,757/1,461,892 · genomes 3,088/152,244 · joint denominator

Ancestry group	Frequency	1 in
African / African-Americangrpmax	7.12%	14
Middle Eastern	0.825%	121
Admixed American	0.6%	167
Remaining individualsnot grpmax-eligible	0.59%	169
Ashkenazi Jewishnot grpmax-eligible	0.108%	925
European (non-Finnish)	0.056%	1,785
South Asian	0.0329%	3,036
East Asian	0.00223%	44,870

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: APOBEC2
Protein: p.Ser199Pro
Coding: c.595T>C
MANE Select: NM_006789
dbSNP: rs114127156
Type: single nucleotide variant
Location: chr6:41061791 (GRCh38)
Gene constraint: LOEUF 1.085 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 73.10 · 1 PDB

Full APOBEC2 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Similar variants

APOBEC2 p.Ala2Asp Uncertain significance ★ ⚠ same type
APOBEC2 p.Ala8Val Uncertain significance ★ ⚠ same type
APOBEC2 p.Ala95Val Uncertain significance ★ ⚠ same type
APOBEC2 p.Arg116Trp Uncertain significance ★ ⚠ same type
APOBEC2 p.Arg46Gln Uncertain significance ★ ⚠ same type
APOBEC2 p.Arg46Trp Uncertain significance ★ ⚠ same type
APOBEC2 p.Arg57Trp Uncertain significance ★ ⚠ same type
APOBEC2 p.Arg87Trp 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/apobec2-p-ser199pro (accessed [today's date]).

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