Is INS p.Ala24= (c.72C>A) pathogenic?

INS p.Ala24= (c.72C>A) is classified Benign/Likely benign in INS (ClinVar, Multiple submitters, 5 submitters; last evaluated 2025-03-05). Ultra-rare (popmax 0.0659%, sas); Associated with Transient Neonatal Diabetes, Dominant/Recessive.

What condition is associated with INS p.Ala24= (c.72C>A)?

INS p.Ala24= (c.72C>A) is associated with Transient Neonatal Diabetes, Dominant/Recessive, maturity-onset diabetes of the young type 10 (ClinVar).

How common is INS p.Ala24= (c.72C>A) in the general population?

INS p.Ala24= (c.72C>A) is ultra-rare (popmax 0.0659%, sas) (gnomAD).

INS p.Ala24=

c.72C>A · rs539284976 · VCV880304

Benign/Likely benign Multiple submitters

Classification

Benign/Likely benign

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 5 submitters

gnomAD v4.1

Rare

ultra-rare (popmax 0.0659%, sas)

Conditions

Transient Neonatal Diabetes, Dominant/Recessive

Computational evidence

Protein change
Missense predictors do not apply to this variant type; conservation carries the signal.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 2.6	GERP -0.15, phastCons 1
Overall
CADD	5.451	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.0659% South Asian · 60/91,090 alleles

Filtering AF 0.0525% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.0476%

Overall 0.00409% 66/1,612,696 alleles · ultra-rare exomes 61/1,460,354 · genomes 5/152,342 · joint denominator

Ancestry group	Frequency	1 in
South Asiangrpmax	0.0659%	1,518
Remaining individualsnot grpmax-eligible	0.00961%	10,410

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.Ala24=
Coding: c.72C>A
MANE Select: NM_000207
dbSNP: rs539284976
Type: single nucleotide variant
Location: chr11:2160900 (GRCh38)
Gene constraint: LOEUF 1.195 · pLI 0.02 · ClinGen HI 0/3 (gnomAD)
Structure: AlphaFold pLDDT 53.19 · 386 PDB
Residue 24: a UniProt-annotated variant site (in pndm4)

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

Disease context

Transient Neonatal Diabetes, Dominant/Recessive

Also linked: maturity-onset diabetes of the young type 10

Similar variants

INS p.Ala24Val Likely pathogenic ★★ ⚠ same residue
INS c.-152C>A Pathogenic/Likely pathogenic ★★ same condition
INS c.-152C>G Pathogenic ★★ same condition
INS p.Arg89Cys Pathogenic/Likely pathogenic ★★ same condition
INS p.Arg89His Pathogenic/Likely pathogenic ★★ same condition
INS p.Gly32Ser Pathogenic/Likely pathogenic ★★ ⚠ same condition
INS p.Met1Val Pathogenic/Likely pathogenic ★★ same condition
INS p.Val42Ala Pathogenic/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-ala24 (accessed [today's date]).

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