Is ABCG5 p.Leu412= (c.1234C>T) pathogenic?

ABCG5 p.Leu412= (c.1234C>T) is classified Likely benign in ABCG5 (ClinVar, Single submitter, 1 submitter; last evaluated 2020-10-25). Very rare (popmax 8.47e-05%, nfe); Associated with Cardiovascular phenotype.

What condition is associated with ABCG5 p.Leu412= (c.1234C>T)?

ABCG5 p.Leu412= (c.1234C>T) is associated with Cardiovascular phenotype (ClinVar).

How common is ABCG5 p.Leu412= (c.1234C>T) in the general population?

ABCG5 p.Leu412= (c.1234C>T) is very rare (popmax 8.47e-05%, nfe) (gnomAD).

ABCG5 p.Leu412=

c.1234C>T · rs2466001084 · VCV1756399

Likely benign Single submitter

Classification

Likely benign

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

gnomAD v4.1

Rare

very rare (popmax 8.47e-05%, nfe)

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 2.1	GERP -2.7, phastCons 0.65
Overall
CADD	3.257	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 8.47e-05% European (non-Finnish) · 1/1,180,046 alleles

Overall 6.84e-05% 1/1,461,884 alleles · very rare

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.Leu412=
Coding: c.1234C>T
MANE Select: NM_022436
dbSNP: rs2466001084
Type: single nucleotide variant
Location: chr2:43824003 (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 412: the abc transmembrane type-2 domain; a turn

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.Leu412Val 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-leu412 (accessed [today's date]).

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