Is ABCG1 p.Ala456= (c.1368G>C) pathogenic?

ABCG1 p.Ala456= (c.1368G>C) is classified Benign in ABCG1 (ClinVar, Multiple submitters, 3 submitters; last evaluated 2018-08-09). Common (popmax 8.51%, afr) — too common for a highly-penetrant pathogenic allele.

ABCG1 p.Ala456=

Q: How common is ABCG1 p.Ala456= (c.1368G>C) in the general population?

ABCG1 p.Ala456= (c.1368G>C) is common (popmax 8.51%, afr) — too common for a highly-penetrant pathogenic allele (gnomAD).

c.1368G>C · rs61735842 · VCV786373

Benign Multiple submitters

Classification

Benign

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 3 submitters

gnomAD v4.1

Common

common (popmax 8.51%, 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.
REVEL	0.069	moderately benign-leaning
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP -20	GERP -4.3
Overall
CADD	0.012	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 8.51% African / African-American · 6,382/74,952 alleles

Filtering AF 8.34% ClinGen BA1/BS1 input FAF95, joint · FAF99 8.27%

Overall 0.454% 7,326/1,614,032 alleles · common

Ancestry group	Frequency	1 in
African / African-Americangrpmax	8.51%	12
Admixed American	0.72%	139
Remaining individualsnot grpmax-eligible	0.571%	175
Middle Eastern	0.181%	551
South Asian	0.011%	9,107
European (non-Finnish)	0.0106%	9,440
Finnishnot grpmax-eligible	0.00937%	10,669
Ashkenazi Jewishnot grpmax-eligible	0.00676%	14,802
East Asian	0.00223%	44,888

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: ABCG1
Protein: p.Ala456=
Coding: c.1368G>C
MANE Select: NM_016818
dbSNP: rs61735842
Type: single nucleotide variant
Location: chr21:42290193 (GRCh38)
Gene constraint: LOEUF 0.573 · pLI 0.20 (gnomAD)
Structure: AlphaFold pLDDT 81.34 · 5 PDB
Residue 456: the abc transmembrane type-2 domain; an α-helix

Full ABCG1 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Similar variants

ABCG1 p.Leu643= Likely benign ★★ same type
ABCG1 p.Pro149= Benign ★★ same type
ABCG1 p.Ser547= Benign ★★ same type
ABCG1 c.1122+21A>C Uncertain significance ★ ⚠ same type
ABCG1 c.1122+24G>C Uncertain significance ★ ⚠ same type
ABCG1 c.1122+2T>C Uncertain significance ★ ⚠ same type
ABCG1 p.Ala546Thr Uncertain significance ★ ⚠ same type
ABCG1 p.Arg222Cys 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/abcg1-p-ala456 (accessed [today's date]).

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