Is ABCG4 p.Lys178= (c.534G>A) pathogenic?

ABCG4 p.Lys178= (c.534G>A) is classified Benign in ABCG4 (ClinVar, Multiple submitters, 2 submitters; last evaluated 2018-04-16). Common (popmax 9.02%, afr) — too common for a highly-penetrant pathogenic allele.

ABCG4 p.Lys178=

Q: How common is ABCG4 p.Lys178= (c.534G>A) in the general population?

ABCG4 p.Lys178= (c.534G>A) is common (popmax 9.02%, afr) — too common for a highly-penetrant pathogenic allele (gnomAD).

c.534G>A · rs12277959 · VCV773016

Benign Multiple submitters

Classification

Benign

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 2 submitters

gnomAD v4.1

Common

common (popmax 9.02%, 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	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 3.7	GERP -1.5, phastCons 1
Overall
CADD	9.261	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 9.02% African / African-American · 6,765/74,982 alleles

Filtering AF 8.84% ClinGen BA1/BS1 input FAF95, joint · FAF99 8.77%

Overall 0.484% 7,812/1,613,394 alleles · common exomes 4,005/1,461,012 · genomes 3,807/152,382 · joint denominator

Ancestry group	Frequency	1 in
African / African-Americangrpmax	9.02%	11
Remaining individualsnot grpmax-eligible	0.73%	137
Admixed American	0.705%	142
Middle Eastern	0.496%	202
South Asian	0.0297%	3,370
European (non-Finnish)	0.00958%	10,441

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: ABCG4
Protein: p.Lys178=
Coding: c.534G>A
MANE Select: NM_022169
dbSNP: rs12277959
Type: single nucleotide variant
Location: chr11:119154569 (GRCh38)
Gene constraint: LOEUF 0.694 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 83.69
Residue 178: the abc transporter domain

Full ABCG4 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Similar variants

ABCG4 p.Asn345= Benign ★★ same type
ABCG4 p.Pro352Leu Benign ★★ same type
ABCG4 p.Ala17Pro Uncertain significance ★ ⚠ same type
ABCG4 p.Ala19Thr Uncertain significance ★ ⚠ same type
ABCG4 p.Ala19Val Uncertain significance ★ ⚠ same type
ABCG4 p.Ala212Thr Uncertain significance ★ ⚠ same type
ABCG4 p.Ala234Ser Uncertain significance ★ ⚠ same type
ABCG4 p.Ala28Thr 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/abcg4-p-lys178 (accessed [today's date]).

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