Is ABCG5 p.Ser46fs (c.136del) pathogenic?

ABCG5 p.Ser46fs (c.136del) is classified Pathogenic in ABCG5 (ClinVar, Multiple submitters, 2 submitters; last evaluated 2025-06-18). No gnomAD frequency available for this variant; Associated with Cardiovascular phenotype.

What condition is associated with ABCG5 p.Ser46fs (c.136del)?

ABCG5 p.Ser46fs (c.136del) is associated with Cardiovascular phenotype, sitosterolemia (ClinVar).

How common is ABCG5 p.Ser46fs (c.136del) in the general population?

ABCG5 p.Ser46fs (c.136del) is no gnomAD frequency available for this variant (gnomAD).

ABCG5 p.Ser46fs

c.136del · rs2466150084 · VCV1771014

Pathogenic Multiple submitters

Classification

Pathogenic

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 2 submitters

Consequence

frameshift

predicted LoF

gnomAD v4.1

Not reported

no gnomAD frequency available for this variant

Conditions

Cardiovascular phenotype

Computational evidence

Protein change
Missense predictors do not apply to this variant type; conservation carries the signal.
Consequence	frameshift	predicted loss-of-function
NMD	predicted	premature termination codon in exon 1 of 13
Splicing
SpliceAI	—	not assessed · substitutions only
Constraint at this position
Conservation	phyloP 1.6	GERP 0.69, phastCons 0.87

Predicted loss-of-function is descriptive, not an applied PVS1 code.

Population frequency

dbSNP / gnomAD

No gnomAD frequency available for this variant. This is missing data, not an absence: the variant may or may not be present in gnomAD. Rarity (ACMG PM2) and BA1/BS1 cannot be assessed for it.

Variant & gene context

Gene: ABCG5
Protein: p.Ser46fs
Coding: c.136del
MANE Select: NM_022436
dbSNP: rs2466150084
Type: Deletion
Location: chr2:43838544 (GRCh38)
Gene constraint: LOEUF 1.219 · pLI <0.01 · ClinGen HI gene assoc. with recessive phenotype (gnomAD)
Structure: AlphaFold pLDDT 85.48 · 8 PDB

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

Also linked: sitosterolemia

Similar variants

ABCG5 p.Ser46= Likely benign ★★ same residue
ABCG5 p.Gly192fs Pathogenic/Likely pathogenic ★★ same condition
ABCG5 p.Thr108fs Pathogenic ★★ same condition
ABCG5 c.501+16del Benign/Likely benign ★★ same condition
ABCG5 c.1323_1324+2del Likely pathogenic ★ same condition
ABCG5 c.1324_1324+15del Likely pathogenic ★ same condition
ABCG5 c.635-153_1588del Likely pathogenic ★ same condition
ABCG5 p.Ala497fs 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-ser46fs (accessed [today's date]).

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