Is ABCC8 p.Val1207Ile (c.3619G>A) pathogenic?

ABCC8 p.Val1207Ile (c.3619G>A) is classified Uncertain significance in ABCC8 (ClinVar, Multiple submitters, 3 submitters; last evaluated 2025-11-23). AlphaMissense: likely benign (0.0968); Very rare (popmax 0.00223%, eas); Associated with Inborn genetic diseases.

What condition is associated with ABCC8 p.Val1207Ile (c.3619G>A)?

ABCC8 p.Val1207Ile (c.3619G>A) is associated with Inborn genetic diseases (ClinVar).

How common is ABCC8 p.Val1207Ile (c.3619G>A) in the general population?

ABCC8 p.Val1207Ile (c.3619G>A) is very rare (popmax 0.00223%, eas) (gnomAD).

What do computational predictors say about ABCC8 p.Val1207Ile (c.3619G>A)?

AlphaMissense predicts likely benign (score 0.0968) — an in-silico prediction, not a clinical call.

ABCC8 p.Val1207Ile

c.3619G>A · rs1227230033 · VCV1700849

Uncertain significance Multiple submitters

Classification

Uncertain significance

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 3 submitters

AlphaMissense

likely benign

0.0968 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 0.00223%, eas)

Missense predictors

0/3 damaging

AlphaMissense, REVEL, SaProt

Conditions

Inborn genetic diseases

Computational evidence

Protein change
AlphaMissense	0.0968	likely benign
REVEL	0.265	benign-leaning
SaProt	LLR -6.01	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 3.9	GERP 2.8, phastCons 1
Regional constraint	o/e 0.84	unconstrained · MANE · 84 kb · p 1.4e-12 · regional, not allelic
Overall
CADD	22.4	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 0.00223% East Asian · 1/44,890 alleles

Filtering AF 7.9e-05% ClinGen BA1/BS1 input FAF95, joint · FAF99 5.4e-05%

Overall 0.000434% 7/1,614,090 alleles · very rare

Ancestry group	Frequency	1 in
East Asiangrpmax	0.00223%	44,890
Admixed American	0.00167%	60,004
South Asian	0.0011%	91,092
European (non-Finnish)	0.000339%	295,011

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.Val1207Ile
Coding: c.3619G>A
MANE Select: NM_000352
dbSNP: rs1227230033
Type: single nucleotide variant
Location: chr11:17402692 (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 1207: an α-helix; the abc transmembrane type-1 2 domain

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

Disease context

Inborn genetic diseases — disease report on Sugi Atlas → Associated genes, phenotypes, clinical trials & treatments

Similar variants

ABCC8 p.Arg1250Ter Pathogenic ★★ same condition
ABCC8 c.1923+3G>A Uncertain significance ★★ same condition
ABCC8 p.Ala365Val Uncertain significance ★★ ⚠ same condition
ABCC8 p.Ala478Ser Uncertain significance ★★ ⚠ same condition
ABCC8 p.Arg657Gln Uncertain significance ★★ ⚠ same condition
ABCC8 p.Arg992Pro Uncertain significance ★★ ⚠ same condition
ABCC8 p.Asp325Asn Uncertain significance ★★ ⚠ same condition
ABCC8 p.Asp760Glu Uncertain significance ★★ ⚠ 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-val1207ile (accessed [today's date]).

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