Is ABCB7 p.Ala580= (c.1740A>G) pathogenic?

ABCB7 p.Ala580= (c.1740A>G) is classified Benign/Likely benign in ABCB7 (ClinVar, Multiple submitters, 5 submitters; last evaluated 2026-01-26). Common (popmax 39%, afr) — too common for a highly-penetrant pathogenic allele.

ABCB7 p.Ala580=

Q: How common is ABCB7 p.Ala580= (c.1740A>G) in the general population?

ABCB7 p.Ala580= (c.1740A>G) is common (popmax 39%, afr) — too common for a highly-penetrant pathogenic allele (gnomAD).

c.1740A>G · rs1340990 · VCV136246

Benign/Likely benign Multiple submitters

Classification

Benign/Likely benign

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 5 submitters

gnomAD v4.1

Common

common (popmax 39%, 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 -1.7	GERP -3.3
Overall
CADD	4.766	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 39% African / African-American · 22,054/56,619 alleles

Filtering AF 38.5% ClinGen BA1/BS1 input FAF95, joint · FAF99 38.3%

Overall 2.09% 25,224/1,207,216 alleles · common

Ancestry group	Frequency	1 in
African / African-Americangrpmax	39%	3
Remaining individualsnot grpmax-eligible	2.93%	34
Admixed American	2.55%	39
Middle Eastern	1.68%	60
South Asian	0.104%	962
European (non-Finnish)	0.054%	1,854
East Asian	0.00296%	33,736

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: ABCB7
Protein: p.Ala580=
Coding: c.1740A>G
MANE Select: NM_001271696
dbSNP: rs1340990
Type: single nucleotide variant
Location: chrX:75065161 (GRCh38)
Structure: AlphaFold pLDDT 78.19 · 4 PDB
Residue 580: the abc transporter domain; a UniProt-annotated variant site (in); an α-helix

Full ABCB7 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Similar variants

ABCB7 p.Ala580Val Benign/Likely benign ★★ ⚠ same residue
ABCB7 p.Ala580Thr Conflicting classifications of pathogenicity ★ ⚠ same residue
ABCB7 c.1659+5T>G Uncertain significance ★★ same type
ABCB7 c.1935+5G>C Uncertain significance ★★ same type
ABCB7 p.Ala5Glu Uncertain significance ★★ ⚠ same type
ABCB7 p.Arg711His Uncertain significance ★★ ⚠ same type
ABCB7 p.Asn378Asp Uncertain significance ★★ ⚠ same type
ABCB7 p.Asp653Asn 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/abcb7-p-ala580 (accessed [today's date]).

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