What condition is associated with INS p.Pro52Arg (c.155C>G)?

INS p.Pro52Arg (c.155C>G) is associated with Neonatal insulin-dependent diabetes mellitus (ClinVar).

How common is INS p.Pro52Arg (c.155C>G) in the general population?

INS p.Pro52Arg (c.155C>G) is very rare (popmax 0.0011%, sas) (gnomAD).

What do computational predictors say about INS p.Pro52Arg (c.155C>G)?

AlphaMissense predicts likely pathogenic (score 0.5833) — an in-silico prediction, not a clinical call.

INS p.Pro52Arg

Q: Is INS p.Pro52Arg (c.155C>G) pathogenic?

INS p.Pro52Arg (c.155C>G) is classified Likely pathogenic in INS (ClinVar, Single submitter, 1 submitter). AlphaMissense: likely pathogenic (0.5833); Very rare (popmax 0.0011%, sas); Associated with Neonatal insulin-dependent diabetes mellitus.

c.155C>G · rs145038693 · VCV1801850

Likely pathogenic Single submitter

Classification

Likely pathogenic

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely pathogenic

0.5833 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 0.0011%, sas)

Missense predictors

2/3 damaging

AlphaMissense, REVEL, SaProt

Conditions

Neonatal insulin-dependent diabetes mellitus

Computational evidence

Protein change
AlphaMissense	0.5833	likely pathogenic ✓ concordant with ClinVar
REVEL	0.658	pathogenic-leaning
SaProt	LLR -9.28	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 11	GERP 1.2, phastCons 1
Regional constraint	o/e 0.92	unconstrained · MANE · 1,060 bp · p 0.36 · regional, not allelic
Overall
CADD	25.8	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

Grpmax group 0.0011% South Asian · 1/91,086 alleles

Overall 6.2e-05% 1/1,612,472 alleles · very rare exomes 0/1,460,280 · genomes 1/152,192 · joint denominator

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: INS
Protein: p.Pro52Arg
Coding: c.155C>G
MANE Select: NM_000207
dbSNP: rs145038693
Type: single nucleotide variant
Location: chr11:2160817 (GRCh38)
Gene constraint: LOEUF 1.195 · pLI 0.02 · ClinGen HI 0/3 (gnomAD)
Structure: AlphaFold pLDDT 53.19 · 386 PDB
Residue 52: an α-helix

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

Disease context

Neonatal insulin-dependent diabetes mellitus — disease report on Sugi Atlas → Associated genes, phenotypes, clinical trials & treatments

Similar variants

INS p.Pro52His Uncertain significance ★ ⚠ same residue
INS c.188-220C>T Benign/Likely benign ★★ same condition
INS c.-18+21C>T Benign/Likely benign ★★ same condition
TH c.*277G>A Benign/Likely benign ★★ same condition
TH p.Thr426= Benign/Likely benign ★★ same condition
INS c.188-96G>A Conflicting classifications of pathogenicity ★ same condition
INS c.-18+22G>A Conflicting classifications of pathogenicity ★ same condition
INS c.-39A>C Conflicting classifications of pathogenicity ★ 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-pro52arg (accessed [today's date]).

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