Is ABCG8 p.Leu52Val (c.154C>G) pathogenic?

ABCG8 p.Leu52Val (c.154C>G) is classified Benign/Likely benign in ABCG8 (ClinVar, Multiple submitters, 8 submitters; last evaluated 2026-03-01). AlphaMissense: likely benign (0.1269); Low-frequency (popmax 2.02%, afr); Associated with sitosterolemia 1.

What condition is associated with ABCG8 p.Leu52Val (c.154C>G)?

ABCG8 p.Leu52Val (c.154C>G) is associated with sitosterolemia 1 (ClinVar).

How common is ABCG8 p.Leu52Val (c.154C>G) in the general population?

ABCG8 p.Leu52Val (c.154C>G) is low-frequency (popmax 2.02%, afr) (gnomAD).

How is Sitosterolemia inherited?

Typically Autosomal recessive (Orphanet). A genetic counselor can assess individual risk for a family.

What do computational predictors say about ABCG8 p.Leu52Val (c.154C>G)?

AlphaMissense predicts likely benign (score 0.1269) — an in-silico prediction, not a clinical call.

ABCG8 p.Leu52Val

c.154C>G · rs142250628 · VCV767793

Benign/Likely benign Multiple submitters

Classification

Benign/Likely benign

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 8 submitters

AlphaMissense

likely benign

0.1269 · ACMG-weighted

gnomAD v4.1

Rare

low-frequency (popmax 2.02%, afr)

Missense predictors

0/2 damaging

AlphaMissense, SaProt · REVEL no call

Conditions

sitosterolemia 1

Computational evidence

Protein change
AlphaMissense	0.1269	likely benign
REVEL	0.463	indeterminate
SaProt	LLR -8.60	tolerated
⇒ AlphaMissense and SaProt both call this tolerated; REVEL makes no call.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 7.6	GERP 1.5, phastCons 1
Regional constraint	o/e 1.29	unconstrained · MANE · 39 kb · p 8.8e-18 · regional, not allelic
Overall
CADD	24.5	PHRED · no single calibrated threshold — expert panels disagree

AlphaMissense carries the ACMG weight for missense; REVEL and SaProt are independent agreement signals.

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 2.02% African / African-American · 1,512/75,026 alleles

Filtering AF 1.93% ClinGen BA1/BS1 input FAF95, joint · FAF99 1.9%

Overall 0.102% 1,651/1,613,676 alleles · low-frequency

Ancestry group	Frequency	1 in
African / African-Americangrpmax	2.02%	50
Remaining individualsnot grpmax-eligible	0.11%	906
Admixed American	0.085%	1,177
Middle Eastern	0.033%	3,031
European (non-Finnish)	0.00144%	69,390

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.Leu52Val
Coding: c.154C>G
MANE Select: NM_022437
dbSNP: rs142250628
Type: single nucleotide variant
Location: chr2:43844597 (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 52: the abc transporter domain; a β-strand

Full ABCG8 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Disease context

sitosterolemia 1 — disease report on Sugi Atlas → Associated genes, phenotypes, clinical trials & treatments

For Sitosterolemia (Orphanet):

Inheritance: Autosomal recessive
Onset: All ages

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ABCG8 p.Arg412Ter Pathogenic/Likely pathogenic ★★ same condition
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ABCG8 p.Ser107Ter Pathogenic ★★ same condition
ABCG8 p.Trp361Ter 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-leu52val (accessed [today's date]).

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