Is ABCG8 p.Tyr613= (c.1839T>C) pathogenic?

ABCG8 p.Tyr613= (c.1839T>C) is classified Conflicting classifications of pathogenicity in ABCG8 (ClinVar, Conflicting submitters, 7 submitters; last evaluated 2026-01-14). Ultra-rare (popmax 0.0587%, afr); Associated with Cardiovascular phenotype.

What condition is associated with ABCG8 p.Tyr613= (c.1839T>C)?

ABCG8 p.Tyr613= (c.1839T>C) is associated with Cardiovascular phenotype, sitosterolemia 1 (ClinVar).

How common is ABCG8 p.Tyr613= (c.1839T>C) in the general population?

ABCG8 p.Tyr613= (c.1839T>C) is ultra-rare (popmax 0.0587%, afr) (gnomAD).

ABCG8 p.Tyr613=

c.1839T>C · rs147582834 · VCV595310

Conflicting classifications of pathogenicity Conflicting submitters

Classification

Conflicting classifications of pathogenicity

ClinVar

Review

Conflicting submitters ★☆☆☆

ClinVar · 7 submitters

gnomAD v4.1

Rare

ultra-rare (popmax 0.0587%, 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 -2.2	GERP -3.2
Overall
CADD	0.224	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.0587% African / African-American · 44/75,016 alleles

Filtering AF 0.0448% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.04%

Overall 0.0278% 448/1,614,130 alleles · ultra-rare

Ancestry group	Frequency	1 in
African / African-Americangrpmax	0.0587%	1,705
European (non-Finnish)	0.0326%	3,065
Middle Eastern	0.0165%	6,062
Remaining individualsnot grpmax-eligible	0.016%	6,251
Admixed American	0.00833%	12,004
Ashkenazi Jewishnot grpmax-eligible	0.00338%	29,604
South Asian	0.0022%	45,542

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: ABCG8
Protein: p.Tyr613=
Coding: c.1839T>C
MANE Select: NM_022437
dbSNP: rs147582834
Type: single nucleotide variant
Location: chr2:43877643 (GRCh38)
Gene constraint: LOEUF 1.329 · pLI <0.01 · ClinGen HI gene assoc. with recessive phenotype (gnomAD)
Structure: AlphaFold pLDDT 80.94 · 8 PDB
Residue 613: the abc transmembrane type-2 domain

Full ABCG8 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

Also linked: sitosterolemia 1

Similar variants

ABCG8 p.Tyr613His Uncertain significance ★★ ⚠ same residue
ABCG8 c.64-2A>G Pathogenic ★★ same condition
ABCG8 c.965-1G>C Pathogenic ★★ same condition
ABCG8 p.Arg121Ter Pathogenic ★★ same condition
ABCG8 p.Arg164Ter Pathogenic ★★ same condition
ABCG8 p.Arg405Cys Pathogenic/Likely pathogenic ★★ ⚠ same condition
ABCG8 p.Arg412Ter Pathogenic/Likely pathogenic ★★ same condition
ABCG8 p.Gln271Ter Pathogenic/Likely pathogenic ★★ 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/abcg8-p-tyr613 (accessed [today's date]).

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