Is ABCC8 p.Asp310Val (c.929A>T) pathogenic?

ABCC8 p.Asp310Val (c.929A>T) is classified Uncertain significance in ABCC8 (ClinVar, Multiple submitters, 2 submitters; last evaluated 2023-08-16). AlphaMissense: likely pathogenic (0.9873); Absent from gnomAD v4.1; Associated with ABCC8-related disorder.

What condition is associated with ABCC8 p.Asp310Val (c.929A>T)?

ABCC8 p.Asp310Val (c.929A>T) is associated with ABCC8-related disorder, hyperinsulinemic hypoglycemia, familial, 1 (ClinVar).

How common is ABCC8 p.Asp310Val (c.929A>T) in the general population?

ABCC8 p.Asp310Val (c.929A>T) is absent from gnomAD v4.1 (gnomAD).

What do computational predictors say about ABCC8 p.Asp310Val (c.929A>T)?

AlphaMissense predicts likely pathogenic (score 0.9873) — an in-silico prediction, not a clinical call.

ABCC8 p.Asp310Val

c.929A>T · rs761869476 · VCV2576215

Uncertain significance Multiple submitters

Classification

Uncertain significance

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 2 submitters

AlphaMissense

likely pathogenic

0.9873 · ACMG-weighted

gnomAD v4.1

Absent

absent from gnomAD v4.1

Missense predictors

2/3 damaging

AlphaMissense, REVEL, SaProt

Conditions

ABCC8-related disorder

Computational evidence

Protein change
AlphaMissense	0.9873	likely pathogenic · top 9% in ABCC8
REVEL	0.978	strongly pathogenic-leaning
SaProt	LLR -9.64	tolerated
⇒ AlphaMissense and REVEL call this damaging; SaProt does not.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 7.9	GERP 2.3, phastCons 1
Regional constraint	o/e 0.84	unconstrained · MANE · 84 kb · p 1.4e-12 · regional, not allelic
Overall
CADD	27.9	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

Absent from gnomAD v4.1. Not observed in any sequenced alleles — a rarity signal (ACMG PM2-supporting), not evidence of pathogenicity on its own.

Variant & gene context

Gene: ABCC8
Protein: p.Asp310Val
Coding: c.929A>T
MANE Select: NM_000352
dbSNP: rs761869476
Type: single nucleotide variant
Location: chr11:17460570 (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 310: an α-helix; the abc transmembrane type-1 1 domain; a UniProt-annotated variant site (in hhf1)

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

Disease context

ABCC8-related disorder

Also linked: hyperinsulinemic hypoglycemia, familial, 1

Similar variants

ABCC8 p.Asp310Asn Likely pathogenic ★★ 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-asp310val (accessed [today's date]).

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