Is ABCG5 p.Ala478Asp (c.1433C>A) pathogenic?

ABCG5 p.Ala478Asp (c.1433C>A) is classified Uncertain significance in ABCG5 (ClinVar, Single submitter, 1 submitter; last evaluated 2021-07-08). AlphaMissense: likely pathogenic (0.8495); Absent from gnomAD v4.1; Associated with Cardiovascular phenotype.

What condition is associated with ABCG5 p.Ala478Asp (c.1433C>A)?

ABCG5 p.Ala478Asp (c.1433C>A) is associated with Cardiovascular phenotype (ClinVar).

How common is ABCG5 p.Ala478Asp (c.1433C>A) in the general population?

ABCG5 p.Ala478Asp (c.1433C>A) is absent from gnomAD v4.1 (gnomAD).

What do computational predictors say about ABCG5 p.Ala478Asp (c.1433C>A)?

AlphaMissense predicts likely pathogenic (score 0.8495) — an in-silico prediction, not a clinical call.

ABCG5 p.Ala478Asp

c.1433C>A · rs2465984821 · VCV1772548

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely pathogenic

0.8495 · ACMG-weighted

gnomAD v4.1

Absent

absent from gnomAD v4.1

Missense predictors

1/2 damaging

AlphaMissense, SaProt · REVEL no call

Conditions

Cardiovascular phenotype

Computational evidence

Protein change
AlphaMissense	0.8495	likely pathogenic · top 8% in ABCG5
REVEL	0.458	indeterminate
SaProt	LLR -9.62	tolerated
⇒ AlphaMissense calls this damaging; SaProt does not; REVEL makes no call.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 6	GERP 0.87, phastCons 1
Regional constraint	o/e 1.09	unconstrained · MANE · 26 kb · p 0.0064 · regional, not allelic
Overall
CADD	23.1	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

Absent from gnomAD v4.1. Not observed in any sequenced alleles — a rarity signal (ACMG PM2-supporting), not evidence of pathogenicity on its own.

Variant & gene context

Gene: ABCG5
Protein: p.Ala478Asp
Coding: c.1433C>A
MANE Select: NM_022436
dbSNP: rs2465984821
Type: single nucleotide variant
Location: chr2:43822827 (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 478: the abc transmembrane type-2 domain; an α-helix

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.Ala478Thr Conflicting classifications of pathogenicity ★ ⚠ same residue
ABCG5 p.Ala478= Likely benign 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

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-ala478asp (accessed [today's date]).

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