Is ABCC8 p.Pro201Leu (c.602C>T) pathogenic?

ABCC8 p.Pro201Leu (c.602C>T) is classified Conflicting classifications of pathogenicity in ABCC8 (ClinVar, Conflicting submitters, 3 submitters; last evaluated 2025-10-27). AlphaMissense: likely benign (0.2369); Very rare (popmax 0.0011%, sas); Associated with hyperinsulinemic hypoglycemia, familial, 1.

What condition is associated with ABCC8 p.Pro201Leu (c.602C>T)?

ABCC8 p.Pro201Leu (c.602C>T) is associated with hyperinsulinemic hypoglycemia, familial, 1 (ClinVar).

How common is ABCC8 p.Pro201Leu (c.602C>T) in the general population?

ABCC8 p.Pro201Leu (c.602C>T) is very rare (popmax 0.0011%, sas) (gnomAD).

What do computational predictors say about ABCC8 p.Pro201Leu (c.602C>T)?

AlphaMissense predicts likely benign (score 0.2369) — an in-silico prediction, not a clinical call.

ABCC8 p.Pro201Leu

c.602C>T · rs933815442 · VCV802660

Conflicting classifications of pathogenicity Conflicting submitters

Classification

Conflicting classifications of pathogenicity

ClinVar

Review

Conflicting submitters ★☆☆☆

ClinVar · 3 submitters

AlphaMissense

likely benign

0.2369 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 0.0011%, sas)

Missense predictors

0/2 damaging

AlphaMissense, SaProt · REVEL no call

Conditions

hyperinsulinemic hypoglycemia, familial, 1

Computational evidence

Protein change
AlphaMissense	0.2369	likely benign
REVEL	0.616	indeterminate
SaProt	LLR -7.59	tolerated
⇒ AlphaMissense and SaProt both call this tolerated; REVEL makes no call.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 12	GERP 1.4, phastCons 1
Regional constraint	o/e 0.84	unconstrained · MANE · 84 kb · p 1.4e-12 · regional, not allelic
Overall
CADD	27.4	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

Grpmax group 0.0011% South Asian · 1/91,050 alleles

Filtering AF 0.000247% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.000159%

Overall 0.000496% 8/1,613,984 alleles · very rare

Ancestry group	Frequency	1 in
South Asiangrpmax	0.0011%	91,050
European (non-Finnish)	0.000593%	168,577

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.Pro201Leu
Coding: c.602C>T
MANE Select: NM_000352
dbSNP: rs933815442
Type: single nucleotide variant
Location: chr11:17461803 (GRCh38)
Gene constraint: LOEUF 0.829 · pLI <0.01 · ClinGen HI gene assoc. with recessive phenotype (gnomAD)
Structure: AlphaFold pLDDT 82.56 · 8 PDB

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

Disease context

hyperinsulinemic hypoglycemia, familial, 1 — disease report on Sugi Atlas → Associated genes, phenotypes, clinical trials & treatments

Similar variants

ABCC8 p.Pro201= Likely benign ★★ same residue
ABCC8 p.Pro201Gln 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

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-pro201leu (accessed [today's date]).

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