Is ABCC8 p.Phe169= (c.507C>T) pathogenic?

ABCC8 p.Phe169= (c.507C>T) is classified Conflicting classifications of pathogenicity in ABCC8 (ClinVar, Conflicting submitters, 3 submitters; last evaluated 2026-01-09). Very rare (popmax 0.00516%, amr); Associated with permanent neonatal diabetes mellitus.

What condition is associated with ABCC8 p.Phe169= (c.507C>T)?

ABCC8 p.Phe169= (c.507C>T) is associated with permanent neonatal diabetes mellitus, hyperinsulinemic hypoglycemia, familial, 1, diabetes mellitus, transient neonatal, 2 (ClinVar).

How common is ABCC8 p.Phe169= (c.507C>T) in the general population?

ABCC8 p.Phe169= (c.507C>T) is very rare (popmax 0.00516%, amr) (gnomAD).

How is Isolated permanent neonatal diabetes mellitus inherited?

Typically Autosomal dominant, Autosomal recessive (Orphanet). A genetic counselor can assess individual risk for a family.

ABCC8 p.Phe169=

c.507C>T · rs755745806 · VCV878978

Conflicting classifications of pathogenicity Conflicting submitters

Classification

Conflicting classifications of pathogenicity

ClinVar

Review

Conflicting submitters ★☆☆☆

ClinVar · 3 submitters

gnomAD v4.1

Rare

very rare (popmax 0.00516%, amr)

Conditions

permanent neonatal diabetes mellitus

Computational evidence

Protein change
Missense predictors do not apply to this variant type; conservation carries the signal.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 8.6	GERP 2.5, phastCons 1
Overall
CADD	15.22	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.00516% Admixed American · 3/58,092 alleles

Filtering AF 0.00137% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.00068%

Overall 0.000187% 3/1,602,068 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.Phe169=
Coding: c.507C>T
MANE Select: NM_000352
dbSNP: rs755745806
Type: single nucleotide variant
Location: chr11:17463510 (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 169: an α-helix

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

Disease context

permanent neonatal diabetes mellitus — disease report on Sugi Atlas → Associated genes, phenotypes, clinical trials & treatments

Also linked: hyperinsulinemic hypoglycemia, familial, 1 diabetes mellitus, transient neonatal, 2 maturity-onset diabetes of the young transient neonatal diabetes mellitus

For Isolated permanent neonatal diabetes mellitus (Orphanet):

Inheritance: Autosomal dominant, Autosomal recessive
Onset: Antenatal, Infancy, Neonatal
Prevalence: 1-9 / 1 000 000 (Europe)

Similar variants

ABCC8 p.Phe169Val Uncertain significance ★ ⚠ same residue
ABCC8 c.1176+2T>C Pathogenic/Likely pathogenic ★★ same condition
ABCC8 c.1333-1013A>G Pathogenic/Likely pathogenic ★★ same condition
ABCC8 c.148+1G>A Pathogenic/Likely pathogenic ★★ same condition
ABCC8 c.148+2T>G Likely pathogenic ★★ same condition
ABCC8 c.1630+1G>A Pathogenic/Likely pathogenic ★★ same condition
ABCC8 c.1630+1G>T Pathogenic ★★ same condition
ABCC8 c.1817+2T>C Pathogenic/Likely 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/abcc8-p-phe169 (accessed [today's date]).

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