Is ABCG2 p.Pro593Ser (c.1777C>T) pathogenic?

ABCG2 p.Pro593Ser (c.1777C>T) is classified Uncertain significance in ABCG2 (ClinVar, Single submitter, 1 submitter; last evaluated 2022-09-06). AlphaMissense: likely benign (0.09); Absent from gnomAD v4.1.

How common is ABCG2 p.Pro593Ser (c.1777C>T) in the general population?

ABCG2 p.Pro593Ser (c.1777C>T) is absent from gnomAD v4.1 (gnomAD).

What do computational predictors say about ABCG2 p.Pro593Ser (c.1777C>T)?

AlphaMissense predicts likely benign (score 0.09) — an in-silico prediction, not a clinical call.

ABCG2 p.Pro593Ser

c.1777C>T · rs2476056506 · VCV2310874

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.09 · ACMG-weighted

gnomAD v4.1

Absent

absent from gnomAD v4.1

Missense predictors

0/3 damaging

AlphaMissense, REVEL, SaProt

Computational evidence

Protein change
AlphaMissense	0.09	likely benign
REVEL	0.178	moderately benign-leaning
SaProt	LLR -4.75	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 1.2	GERP -1, phastCons 0.37
Regional constraint	o/e 1.01	unconstrained · MANE · 48 kb · p 0.73 · regional, not allelic
Overall
CADD	16.96	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

Absent from gnomAD v4.1. Not observed in any sequenced alleles — a rarity signal (ACMG PM2-supporting), not evidence of pathogenicity on its own.

Variant & gene context

Gene: ABCG2
Protein: p.Pro593Ser
Coding: c.1777C>T
MANE Select: NM_004827
dbSNP: rs2476056506
Type: single nucleotide variant
Location: chr4:88094620 (GRCh38)
Gene constraint: LOEUF 1.308 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 85.54 · 29 PDB
Residue 593: the abc transmembrane type-2 domain; a disulfide bond

Full ABCG2 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Similar variants

ABCG2 p.Tyr123= Benign ★★ same type
ABCG2 p.Ala505Gly Uncertain significance ★ ⚠ same type
ABCG2 p.Arg575Gln Uncertain significance ★ ⚠ same type
ABCG2 p.Asn289Lys Uncertain significance ★ ⚠ same type
ABCG2 p.Asp312Gly Uncertain significance ★ ⚠ same type
ABCG2 p.Asp419Tyr Uncertain significance ★ ⚠ same type
ABCG2 p.Gln324His Uncertain significance ★ ⚠ same type
ABCG2 p.Gln393Arg 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/abcg2-p-pro593ser (accessed [today's date]).

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