Is ABCG5 p.Leu207= (c.621G>A) pathogenic?

ABCG5 p.Leu207= (c.621G>A) is classified Likely benign in ABCG5 (ClinVar, Single submitter, 1 submitter; last evaluated 2023-04-09). Very rare (popmax 0.00267%, afr); Associated with Cardiovascular phenotype.

What condition is associated with ABCG5 p.Leu207= (c.621G>A)?

ABCG5 p.Leu207= (c.621G>A) is associated with Cardiovascular phenotype (ClinVar).

How common is ABCG5 p.Leu207= (c.621G>A) in the general population?

ABCG5 p.Leu207= (c.621G>A) is very rare (popmax 0.00267%, afr) (gnomAD).

ABCG5 p.Leu207=

c.621G>A · rs146336941 · VCV2564006

Likely benign Single submitter

Classification

Likely benign

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

gnomAD v4.1

Rare

very rare (popmax 0.00267%, afr)

Conditions

Cardiovascular phenotype

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 0.69	GERP -3.8, phastCons 1
Overall
CADD	4.212	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.00267% African / African-American · 2/74,916 alleles

Filtering AF 0.000443% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.000166%

Overall 0.000248% 4/1,613,966 alleles · very rare

Ancestry group	Frequency	1 in
African / African-Americangrpmax	0.00267%	37,458
Remaining individualsnot grpmax-eligible	0.0016%	62,488
European (non-Finnish)	8.47e-05%	1,180,034

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: ABCG5
Protein: p.Leu207=
Coding: c.621G>A
MANE Select: NM_022436
dbSNP: rs146336941
Type: single nucleotide variant
Location: chr2:43827996 (GRCh38)
Gene constraint: LOEUF 1.219 · pLI <0.01 · ClinGen HI gene assoc. with recessive phenotype (gnomAD)
Structure: AlphaFold pLDDT 85.48 · 8 PDB
Residue 207: the abc transporter domain; an α-helix

Full ABCG5 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Disease context

Cardiovascular phenotype — disease report on Sugi Atlas → Associated genes, phenotypes, clinical trials & treatments

Similar variants

ABCG5 p.Leu207Val Uncertain significance ★ ⚠ same residue
ABCG5 c.1325-1G>T Likely pathogenic ★★ same condition
ABCG5 p.Gln251Ter Pathogenic ★★ same condition
ABCG5 p.Glu146Ter Pathogenic ★★ same condition
ABCG5 p.Ala170Asp Uncertain significance ★★ ⚠ same condition
ABCG5 p.Ala264Val Uncertain significance ★★ ⚠ same condition
ABCG5 p.Ala278Glu Uncertain significance ★★ ⚠ same condition
ABCG5 p.Ala333Ser Uncertain significance ★★ ⚠ same condition

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/abcg5-p-leu207 (accessed [today's date]).

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