Is ABCC8 p.Val1429fs (c.4284del) pathogenic?

ABCC8 p.Val1429fs (c.4284del) is classified Pathogenic in ABCC8 (ClinVar, Single submitter, 1 submitter; last evaluated 2023-09-29). Very rare (popmax 8.69e-05%, nfe).

How common is ABCC8 p.Val1429fs (c.4284del) in the general population?

ABCC8 p.Val1429fs (c.4284del) is very rare (popmax 8.69e-05%, nfe) (gnomAD).

ABCC8 p.Val1429fs

c.4284del · rs2496449904 · VCV2735545

Pathogenic Single submitter

Classification

Pathogenic

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

Consequence

frameshift

predicted LoF

gnomAD v4.1

Rare

very rare (popmax 8.69e-05%, nfe)

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 35 of 39
Splicing
SpliceAI	—	not assessed · substitutions only
Constraint at this position
Conservation	phyloP 4.9	GERP 0.012, phastCons 1

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

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 8.69e-05% European (non-Finnish) · 1/1,151,050 alleles

Overall 7.12e-05% 1/1,404,862 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: ABCC8
Protein: p.Val1429fs
Coding: c.4284del
MANE Select: NM_000352
dbSNP: rs2496449904
Type: Deletion
Location: chr11:17395633 (GRCh38)
Gene constraint: LOEUF 0.829 · pLI <0.01 · ClinGen HI gene assoc. with recessive phenotype (gnomAD)
Structure: AlphaFold pLDDT 82.56 · 8 PDB
Residue 1429: the abc transporter 2 domain

Full ABCC8 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Similar variants

ABCC8 p.Val1429Ile Uncertain significance ★★ ⚠ same residue
ABCC8 p.Ala269fs Pathogenic/Likely pathogenic ★★ same type
ABCC8 p.Gln19fs Pathogenic/Likely pathogenic ★★ same type
ABCC8 p.Gln273fs Pathogenic/Likely pathogenic ★★ same type
ABCC8 p.Gln632fs Pathogenic ★★ same type
ABCC8 p.His627fs Pathogenic ★★ same type
ABCC8 p.Ile450fs Pathogenic ★★ same type
ABCC8 p.Ile550fs Pathogenic/Likely pathogenic ★★ same type

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/abcc8-p-val1429fs (accessed [today's date]).

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