Is INS p.Cys109Phe (c.326G>T) pathogenic?

INS p.Cys109Phe (c.326G>T) is classified Likely pathogenic in INS (ClinVar, Single submitter, 1 submitter). AlphaMissense: likely pathogenic (0.9986); Absent from gnomAD v4.1; Associated with neonatal diabetes mellitus.

What condition is associated with INS p.Cys109Phe (c.326G>T)?

INS p.Cys109Phe (c.326G>T) is associated with neonatal diabetes mellitus (ClinVar).

How common is INS p.Cys109Phe (c.326G>T) in the general population?

INS p.Cys109Phe (c.326G>T) is absent from gnomAD v4.1 (gnomAD).

What do computational predictors say about INS p.Cys109Phe (c.326G>T)?

AlphaMissense predicts likely pathogenic (score 0.9986) — an in-silico prediction, not a clinical call.

INS p.Cys109Phe

c.326G>T · rs2133672742 · VCV1526011

Likely pathogenic Single submitter

Classification

Likely pathogenic

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely pathogenic

0.9986 · ACMG-weighted

gnomAD v4.1

Absent

absent from gnomAD v4.1

Missense predictors

3/3 damaging

AlphaMissense, REVEL, SaProt

Conditions

neonatal diabetes mellitus

⚠ Built without this gene's context — gene constraint and dosage, protein structure, pathways, panels and related-variant links were not looked up for this page. why

Computational evidence

Protein change
AlphaMissense	0.9986	likely pathogenic ✓ concordant with ClinVar
REVEL	0.979	strongly pathogenic-leaning
SaProt	LLR -11.87	damaging
⇒ AlphaMissense, REVEL and SaProt all call this damaging.
Splicing
SpliceAI	—	not looked up on this page · why
Constraint at this position
Conservation	phyloP 5.7	GERP 1.1, phastCons 1
Regional constraint	o/e 0.05	constrained · MANE · 55 bp · p 1.6e-05 · regional, not allelic
Overall
CADD	28.7	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

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: INS
Protein: p.Cys109Phe
Coding: c.326G>T
MANE Select: NM_000207
dbSNP: rs2133672742
Type: single nucleotide variant
Location: chr11:2159859 (GRCh38)

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

Disease context

neonatal diabetes mellitus — disease report on Sugi Atlas → Associated genes, phenotypes, clinical trials & treatments

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/ins-p-cys109phe (accessed [today's date]).

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