Is ABCG5 p.Arg419= (c.1257C>T) pathogenic?

ABCG5 p.Arg419= (c.1257C>T) is classified Likely benign in ABCG5 (ClinVar, Single submitter, 1 submitter; last evaluated 2021-11-22). Very rare (popmax 0.00668%, eas); Associated with Cardiovascular phenotype.

What condition is associated with ABCG5 p.Arg419= (c.1257C>T)?

ABCG5 p.Arg419= (c.1257C>T) is associated with Cardiovascular phenotype (ClinVar).

How common is ABCG5 p.Arg419= (c.1257C>T) in the general population?

ABCG5 p.Arg419= (c.1257C>T) is very rare (popmax 0.00668%, eas) (gnomAD).

ABCG5 p.Arg419=

c.1257C>T · rs978671799 · VCV1762051

Likely benign Single submitter

Classification

Likely benign

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

gnomAD v4.1

Rare

very rare (popmax 0.00668%, eas)

Conditions

Cardiovascular phenotype

Computational evidence

Protein change
Missense predictors do not apply to this variant type; conservation carries the signal.
Splicing
SpliceAI	<0.2	all four deltas below 0.2 · G>C here scores Δ0.84 · evaluated, not missing
Constraint at this position
Conservation	phyloP -7.1	GERP -3.9
Overall
CADD	1.108	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.00668% East Asian · 3/44,884 alleles

Filtering AF 0.00177% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.000891%

Overall 0.000434% 7/1,614,202 alleles · very rare

Ancestry group	Frequency	1 in
East Asiangrpmax	0.00668%	14,961
European (non-Finnish)	0.000339%	295,008

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.Arg419=
Coding: c.1257C>T
MANE Select: NM_022436
dbSNP: rs978671799
Type: single nucleotide variant
Location: chr2:43823980 (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 419: the abc transmembrane type-2 domain; a UniProt-annotated variant site (in stsl2; loss of normal maturation of glycan chains); a UniProt-annotated variant site (in stsl2; strongly decreased maturation of glycan chains); 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.Arg419Gly Uncertain significance ★ ⚠ same residue
ABCG5 p.Arg419His Pathogenic ★★ ⚠ same residue
ABCG5 p.Arg419Cys Uncertain significance ★★ ⚠ same residue
ABCG5 p.Arg419Pro Pathogenic 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

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-arg419 (accessed [today's date]).

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