Is ABCC8 p.Val21Phe (c.61G>T) pathogenic?

ABCC8 p.Val21Phe (c.61G>T) is classified Likely pathogenic in ABCC8 (ClinVar, Single submitter, 1 submitter; last evaluated 2023-08-29). AlphaMissense: likely benign (0.234); Absent from gnomAD v4.1.

How common is ABCC8 p.Val21Phe (c.61G>T) in the general population?

ABCC8 p.Val21Phe (c.61G>T) is absent from gnomAD v4.1 (gnomAD).

What do computational predictors say about ABCC8 p.Val21Phe (c.61G>T)?

AlphaMissense predicts likely benign (score 0.234) — an in-silico prediction, not a clinical call.

ABCC8 p.Val21Phe

c.61G>T · rs1176097396 · VCV3014266

Likely pathogenic Single submitter

Classification

Likely pathogenic

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.234 · ACMG-weighted

gnomAD v4.1

Not reported

no allele count reported in gnomAD v4.1 (AN 1,609,932)

Missense predictors

1/3 damaging

AlphaMissense, REVEL, SaProt

Computational evidence

Protein change
AlphaMissense	0.234	likely benign ⚠ discordant with ClinVar
REVEL	0.79	moderately pathogenic-leaning
SaProt	LLR -5.59	tolerated
⇒ REVEL calls this damaging; AlphaMissense and SaProt do not.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 7.4	GERP 2.2, phastCons 1
Regional constraint	o/e 0.84	unconstrained · MANE · 84 kb · p 1.4e-12 · regional, not allelic
Overall
CADD	29.7	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

No allele count reported in gnomAD v4.1 (AN 1,609,932). This is missing data, not an absence: the variant may or may not be present in gnomAD. Rarity (ACMG PM2) and BA1/BS1 cannot be assessed for it.

Variant & gene context

Gene: ABCC8
Protein: p.Val21Phe
Coding: c.61G>T
MANE Select: NM_000352
dbSNP: rs1176097396
Type: single nucleotide variant
Location: chr11:17476716 (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 21: a β-strand; a disulfide bond; a UniProt-annotated variant site (in hhf1)

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

Similar variants

ABCC8 p.Val21Asp Pathogenic/Likely pathogenic ★★ same residue
ABCC8 p.Val21Ile Uncertain significance ★ ⚠ same residue
ABCC8 p.Val21= Likely benign ★ same residue
ABCC8 p.Val21fs Pathogenic/Likely pathogenic ★★ 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

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-val21phe (accessed [today's date]).

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