Is ABCG5 p.Ser319= (c.957C>T) pathogenic?

ABCG5 p.Ser319= (c.957C>T) is classified Conflicting classifications of pathogenicity in ABCG5 (ClinVar, Conflicting submitters, 9 submitters; last evaluated 2026-01-24). Rare (popmax 0.497%, afr); Associated with sitosterolemia.

What condition is associated with ABCG5 p.Ser319= (c.957C>T)?

ABCG5 p.Ser319= (c.957C>T) is associated with sitosterolemia (ClinVar).

How common is ABCG5 p.Ser319= (c.957C>T) in the general population?

ABCG5 p.Ser319= (c.957C>T) is rare (popmax 0.497%, afr) (gnomAD).

How is Sitosterolemia inherited?

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

ABCG5 p.Ser319=

c.957C>T · rs146131711 · VCV289742

Conflicting classifications of pathogenicity Conflicting submitters

Classification

Conflicting classifications of pathogenicity

ClinVar

Review

Conflicting submitters ★☆☆☆

ClinVar · 9 submitters

gnomAD v4.1

Rare

rare (popmax 0.497%, afr)

Conditions

sitosterolemia

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 4	GERP 0.87, phastCons 1
Overall
CADD	7.807	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.497% African / African-American · 373/75,010 alleles

Filtering AF 0.456% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.439%

Overall 0.0273% 441/1,614,120 alleles · rare

Ancestry group	Frequency	1 in
African / African-Americangrpmax	0.497%	201
Admixed American	0.05%	2,001
Remaining individualsnot grpmax-eligible	0.0352%	2,841
Middle Eastern	0.033%	3,031
South Asian	0.00439%	22,770
European (non-Finnish)	0.000847%	118,002

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.Ser319=
Coding: c.957C>T
MANE Select: NM_022436
dbSNP: rs146131711
Type: single nucleotide variant
Location: chr2:43824380 (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 319: an α-helix

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

Disease context

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

For Sitosterolemia (Orphanet):

Inheritance: Autosomal recessive
Onset: All ages

Similar variants

ABCG5 c.1762+1G>A Pathogenic/Likely pathogenic ★★ same condition
ABCG5 c.634+1G>C Likely pathogenic ★★ same condition
ABCG5 c.904+1G>A Pathogenic ★★ same condition
ABCG5 p.Arg183Ter Pathogenic/Likely pathogenic ★★ same condition
ABCG5 p.Arg243Ter Pathogenic ★★ same condition
ABCG5 p.Arg389His Pathogenic/Likely pathogenic ★★ ⚠ same condition
ABCG5 p.Arg408Ter Pathogenic/Likely pathogenic ★★ same condition
ABCG5 p.Arg419His 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/abcg5-p-ser319 (accessed [today's date]).

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