Is A1BG p.Arg333Pro (c.998G>C) pathogenic?

A1BG p.Arg333Pro (c.998G>C) is classified Uncertain significance in A1BG (ClinVar, Single submitter, 1 submitter; last evaluated 2022-08-02). AlphaMissense: likely pathogenic (0.8311); Very rare (popmax 0.00197%, amr).

How common is A1BG p.Arg333Pro (c.998G>C) in the general population?

A1BG p.Arg333Pro (c.998G>C) is very rare (popmax 0.00197%, amr) (gnomAD).

What do computational predictors say about A1BG p.Arg333Pro (c.998G>C)?

AlphaMissense predicts likely pathogenic (score 0.8311) — an in-silico prediction, not a clinical call.

A1BG p.Arg333Pro

c.998G>C · rs1568553352 · VCV2211717

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely pathogenic

0.8311 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 0.00197%, amr)

Missense predictors

2/3 damaging

AlphaMissense, REVEL, SaProt

Computational evidence

Protein change
AlphaMissense	0.8311	likely pathogenic · top 7% in A1BG
REVEL	0.214	benign-leaning
SaProt	LLR -10.17	damaging
⇒ AlphaMissense and SaProt call this damaging; REVEL does not.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 0.39	GERP -0.25, phastCons 1
Regional constraint	o/e 1.03	unconstrained · MANE · 6,412 bp · p 0.49 · regional, not allelic
Overall
CADD	22.8	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 0.00197% Admixed American · 1/50,638 alleles

Overall 7.19e-05% 1/1,390,056 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: A1BG
Protein: p.Arg333Pro
Coding: c.998G>C
MANE Select: NM_130786
dbSNP: rs1568553352
Type: single nucleotide variant
Location: chr19:58350564 (GRCh38)
Gene constraint: LOEUF 1.34 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 86.63
Residue 333: a disulfide bond; the ig-like v-type 4 domain

Full A1BG gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Similar variants

A1BG p.Ala170Thr Uncertain significance ★ ⚠ same type
A1BG p.Ala197Thr Uncertain significance ★ ⚠ same type
A1BG p.Ala295Val Uncertain significance ★ ⚠ same type
A1BG p.Ala308Glu Uncertain significance ★ ⚠ same type
A1BG p.Ala308Thr Uncertain significance ★ ⚠ same type
A1BG p.Ala327Gly Uncertain significance ★ ⚠ same type
A1BG p.Ala335Thr Uncertain significance ★ ⚠ same type
A1BG p.Ala357Glu 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/a1bg-p-arg333pro (accessed [today's date]).

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