Is ABCG5 p.Val113fs (c.335dup) pathogenic?

ABCG5 p.Val113fs (c.335dup) is classified Pathogenic in ABCG5 (ClinVar, Single submitter, 1 submitter; last evaluated 2023-08-24). Very rare (popmax 0.0047%, eas); Associated with Cardiovascular phenotype.

What condition is associated with ABCG5 p.Val113fs (c.335dup)?

ABCG5 p.Val113fs (c.335dup) is associated with Cardiovascular phenotype (ClinVar).

How common is ABCG5 p.Val113fs (c.335dup) in the general population?

ABCG5 p.Val113fs (c.335dup) is very rare (popmax 0.0047%, eas) (gnomAD).

ABCG5 p.Val113fs

c.335dup · rs1470569820 · VCV2616584

Pathogenic Single submitter

Classification

Pathogenic

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

Consequence

frameshift

predicted LoF

gnomAD v4.1

Rare

very rare (popmax 0.0047%, eas)

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 3 of 13
Splicing
SpliceAI	—	not assessed · substitutions only
Constraint at this position
Conservation	phyloP -0.46	GERP -3.5, phastCons 0.039
Overall
CADD	33.0	PHRED · no single calibrated threshold — expert panels disagree

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

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.0047% East Asian · 2/42,584 alleles

Filtering AF 0.000778% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.000291%

Overall 0.000128% 2/1,567,224 alleles · very rare

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.Val113fs
Coding: c.335dup
MANE Select: NM_022436
dbSNP: rs1470569820
Type: Duplication
Location: chr2:43832013 (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 113: the abc transporter domain; a β-strand

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.Val113Glu Uncertain significance ★ ⚠ same residue
ABCG5 p.Val113= Likely benign ★ same residue
ABCG5 c.905-3dup Conflicting classifications of pathogenicity ★ same condition
ABCG5 c.1325-1G>T Likely pathogenic ★★ same condition
ABCG5 p.Gln251Ter Pathogenic ★★ same condition
ABCG5 p.Glu146Ter Pathogenic ★★ same condition
ABCG5 p.Gly192fs Pathogenic/Likely pathogenic ★★ same condition
ABCG5 p.Ser46fs 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-val113fs (accessed [today's date]).

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