Is ABCG2 p.Tyr123= (c.369C>T) pathogenic?

ABCG2 p.Tyr123= (c.369C>T) is classified Benign in ABCG2 (ClinVar, Multiple submitters, 2 submitters; last evaluated 2018-08-17). Common (popmax 6.78%, afr) — too common for a highly-penetrant pathogenic allele.

ABCG2 p.Tyr123=

Q: How common is ABCG2 p.Tyr123= (c.369C>T) in the general population?

ABCG2 p.Tyr123= (c.369C>T) is common (popmax 6.78%, afr) — too common for a highly-penetrant pathogenic allele (gnomAD).

c.369C>T · rs2231139 · VCV787808

Benign Multiple submitters

Classification

Benign

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 2 submitters

gnomAD v4.1

Common

common (popmax 6.78%, afr) — too common for a highly-penetrant pathogenic allele

Computational evidence

Protein change
Missense predictors do not apply to this variant type; conservation carries the signal.
Splicing
SpliceAI	<0.2	all four deltas below 0.2 · G>C here scores Δ0.42 · evaluated, not missing
Constraint at this position
Conservation	phyloP -0.28	GERP -2.4, phastCons 0.001
Overall
CADD	9.821	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 6.78% African / African-American · 5,080/74,962 alleles

Filtering AF 6.62% ClinGen BA1/BS1 input FAF95, joint · FAF99 6.56%

Overall 0.352% 5,675/1,612,572 alleles · common

Ancestry group	Frequency	1 in
African / African-Americangrpmax	6.78%	15
Remaining individualsnot grpmax-eligible	0.413%	242
Admixed American	0.398%	251
Middle Eastern	0.237%	423
East Asian	0.0134%	7,476
South Asian	0.00989%	10,109
European (non-Finnish)	0.00568%	17,603
Finnishnot grpmax-eligible	0.00469%	21,320

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: ABCG2
Protein: p.Tyr123=
Coding: c.369C>T
MANE Select: NM_004827
dbSNP: rs2231139
Type: single nucleotide variant
Location: chr4:88131812 (GRCh38)
Gene constraint: LOEUF 1.308 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 85.54 · 29 PDB
Residue 123: the abc transporter domain; a β-strand

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

Similar variants

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
ABCG2 p.Gln437Arg 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-tyr123 (accessed [today's date]).

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