Is INS p.Ser98Ile (c.293G>T) pathogenic?

INS p.Ser98Ile (c.293G>T) is classified Likely pathogenic in INS (ClinVar, Single submitter, 1 submitter). AlphaMissense: likely pathogenic (0.7876); Absent from gnomAD v4.1; Associated with neonatal diabetes mellitus.

What condition is associated with INS p.Ser98Ile (c.293G>T)?

INS p.Ser98Ile (c.293G>T) is associated with neonatal diabetes mellitus (ClinVar).

How common is INS p.Ser98Ile (c.293G>T) in the general population?

INS p.Ser98Ile (c.293G>T) is absent from gnomAD v4.1 (gnomAD).

What do computational predictors say about INS p.Ser98Ile (c.293G>T)?

AlphaMissense predicts likely pathogenic (score 0.7876) — an in-silico prediction, not a clinical call.

INS p.Ser98Ile

c.293G>T · rs2133672883 · VCV1526009

Likely pathogenic Single submitter

Classification

Likely pathogenic

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely pathogenic

0.7876 · ACMG-weighted

gnomAD v4.1

Absent

absent from gnomAD v4.1

Missense predictors

2/2 damaging

AlphaMissense, SaProt · REVEL no call

Conditions

neonatal diabetes mellitus

Computational evidence

Protein change
AlphaMissense	0.7876	likely pathogenic ✓ concordant with ClinVar
REVEL	0.622	indeterminate
SaProt	LLR -10.32	damaging
⇒ AlphaMissense and SaProt both call this damaging; REVEL makes no call.
Splicing
SpliceAI	<0.2	all four deltas below 0.2 · C>T here scores Δ0.23 · evaluated, not missing
Constraint at this position
Conservation	phyloP 4.6	GERP -1.5, phastCons 0.43
Regional constraint	o/e 0.05	constrained · MANE · 55 bp · p 1.6e-05 · regional, not allelic
Overall
CADD	24.7	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.Ser98Ile
Coding: c.293G>T
MANE Select: NM_000207
dbSNP: rs2133672883
Type: single nucleotide variant
Location: chr11:2159892 (GRCh38)
Gene constraint: LOEUF 1.195 · pLI 0.02 · ClinGen HI 0/3 (gnomAD)
Structure: AlphaFold pLDDT 53.19 · 386 PDB
Residue 98: a disulfide bond

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

Similar variants

INS p.Ala24Val Likely pathogenic ★★ ⚠ same condition
INS p.Arg89Cys Pathogenic/Likely pathogenic ★★ same condition
INS p.Gly32Ser Pathogenic/Likely pathogenic ★★ ⚠ same condition
INS c.188-16C>T Benign/Likely benign ★★ same condition
INS c.-9C>T Benign/Likely benign ★★ same condition
INS p.His34Pro Likely pathogenic ★ ⚠ same condition
INS p.Leu35Met Likely pathogenic ★ same condition
INS p.Tyr108Asp 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/ins-p-ser98ile (accessed [today's date]).

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