Is ABCG2 c.1277+1908T>G pathogenic?

ABCG2 c.1277+1908T>G is classified Benign in ABCG2 (ClinVar, Single submitter, 1 submitter; last evaluated 2019-01-09). Common (popmax 56.5%, eas) — too common for a highly-penetrant pathogenic allele.

ABCG2 c.1277+1908T>G

Q: How common is ABCG2 c.1277+1908T>G in the general population?

ABCG2 c.1277+1908T>G is common (popmax 56.5%, eas) — too common for a highly-penetrant pathogenic allele (gnomAD).

rs2725263 · VCV1267736

Benign Single submitter

Classification

Benign

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

gnomAD v4.1

Common

common (popmax 56.5%, eas) — 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
Splice region	donor +1908	deep intronic (+1908 nt into the intron)
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 0.57	GERP -2
Non-coding constraint	Z 2.35	1 kb window · o/e 0.82 · regional · uncalibrated
Overall
CADD	2.931	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 56.5% East Asian · 2,925/5,174 alleles

Filtering AF 55.3% ClinGen BA1/BS1 input FAF95, joint · FAF99 55.1%

Overall 44% 66,909/152,044 alleles · common

Ancestry group	Frequency	1 in
Ashkenazi Jewishnot grpmax-eligible	59.4%	2
East Asiangrpmax	56.5%	2
Middle Eastern	56.5%	2
European (non-Finnish)	55.7%	2
South Asian	50.5%	2
Amishnot grpmax-eligible	50.2%	2
Admixed American	49.7%	2
Remaining individualsnot grpmax-eligible	48.6%	2
Finnishnot grpmax-eligible	41%	2
African / African-American	19.4%	5

Ashkenazi Jewish shows a higher raw frequency than the grpmax group above it. gnomAD excludes bottlenecked groups — Finnish, Ashkenazi Jewish, Amish and “Remaining individuals” — from grpmax, because founder effects make their frequencies unrepresentative for filtering. The table is sorted by frequency, so an excluded group can sit above the grpmax row.

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
Coding: c.1277+1908T>G
MANE Select: NM_004827
dbSNP: rs2725263
Type: single nucleotide variant
Location: chr4:88105276 (GRCh38)
Gene constraint: LOEUF 1.308 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 85.54 · 29 PDB

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-c-1277-plus-1908t-g (accessed [today's date]).

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