Is ABCC8 p.Pro768Ser (c.2302C>T) pathogenic?

ABCC8 p.Pro768Ser (c.2302C>T) is classified Uncertain significance in ABCC8 (ClinVar, Single submitter, 1 submitter; last evaluated 2026-04-22). AlphaMissense: likely benign (0.1108); Very rare (popmax 0.00667%, afr).

How common is ABCC8 p.Pro768Ser (c.2302C>T) in the general population?

ABCC8 p.Pro768Ser (c.2302C>T) is very rare (popmax 0.00667%, afr) (gnomAD).

What do computational predictors say about ABCC8 p.Pro768Ser (c.2302C>T)?

AlphaMissense predicts likely benign (score 0.1108) — an in-silico prediction, not a clinical call.

ABCC8 p.Pro768Ser

c.2302C>T · VCV4849173

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.1108 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 0.00667%, afr)

Missense predictors

0/3 damaging

AlphaMissense, REVEL, SaProt

Computational evidence

Protein change
AlphaMissense	0.1108	likely benign
REVEL	0.269	benign-leaning
SaProt	LLR -7.02	tolerated
⇒ AlphaMissense, REVEL and SaProt all call this tolerated.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 7.5	GERP -0.9, phastCons 1
Regional constraint	o/e 0.84	unconstrained · MANE · 84 kb · p 1.4e-12 · regional, not allelic
Overall
CADD	19.5	PHRED · no single calibrated threshold — expert panels disagree

ClinVar classifies this uncertain; the computational predictors unanimously lean tolerated — a triage signal, not a reclassification

AlphaMissense carries the ACMG weight for missense; REVEL and SaProt are independent agreement signals.

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.00667% African / African-American · 5/74,944 alleles

Filtering AF 0.00255% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.00161%

Overall 0.000805% 13/1,614,096 alleles · very rare exomes 11/1,461,848 · genomes 2/152,248 · joint denominator

Ancestry group	Frequency	1 in
African / African-Americangrpmax	0.00667%	14,989
Remaining individualsnot grpmax-eligible	0.0016%	62,488
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.Pro768Ser
Coding: c.2302C>T
MANE Select: NM_000352
Type: single nucleotide variant
Location: chr11:17414600 (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 768: the abc transporter 1 domain

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

Similar variants

ABCC8 p.Pro768= Likely benign ★★ same residue
ABCC8 c.1176+2T>C Pathogenic/Likely pathogenic ★★ same type
ABCC8 c.1333-1013A>G Pathogenic/Likely pathogenic ★★ same type
ABCC8 c.148+1G>A Pathogenic/Likely pathogenic ★★ same type
ABCC8 c.148+2T>G Likely pathogenic ★★ same type
ABCC8 c.1630+1G>A Pathogenic/Likely pathogenic ★★ same type
ABCC8 c.1630+1G>T Pathogenic ★★ same type
ABCC8 c.1817+1G>C 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-pro768ser (accessed [today's date]).

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