Is IAPP p.Asn47Ser (c.140A>G) pathogenic?

IAPP p.Asn47Ser (c.140A>G) is classified Uncertain significance in IAPP (ClinVar, Single submitter, 1 submitter; last evaluated 2025-04-28). AlphaMissense: likely benign (0.0957); Absent from gnomAD v4.1.

How common is IAPP p.Asn47Ser (c.140A>G) in the general population?

IAPP p.Asn47Ser (c.140A>G) is absent from gnomAD v4.1 (gnomAD).

What do computational predictors say about IAPP p.Asn47Ser (c.140A>G)?

AlphaMissense predicts likely benign (score 0.0957) — an in-silico prediction, not a clinical call.

IAPP p.Asn47Ser

c.140A>G · VCV4036999

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.0957 · ACMG-weighted

gnomAD v4.1

Absent

absent from gnomAD v4.1

Missense predictors

0/2 damaging

AlphaMissense, SaProt · REVEL no call

Computational evidence

Protein change
AlphaMissense	0.0957	likely benign
REVEL	0.313	indeterminate
SaProt	LLR -6.52	tolerated
⇒ AlphaMissense and SaProt both call this tolerated; REVEL makes no call.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 1.8	GERP 0.25, phastCons 0.022
Regional constraint	o/e 1.08	unconstrained · MANE · 5,071 bp · p 0.4 · regional, not allelic
Overall
CADD	20.2	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

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: IAPP
Protein: p.Asn47Ser
Coding: c.140A>G
MANE Select: NM_000415
Type: single nucleotide variant
Location: chr12:21378296 (GRCh38)
Gene constraint: LOEUF 1.499 · pLI 0.35 (gnomAD)
Structure: AlphaFold pLDDT 78.59 · 80 PDB
Residue 47: an α-helix

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

Similar variants

IAPP p.Arg33Gln Uncertain significance ★ ⚠ same type
IAPP p.Arg73Lys Uncertain significance ★ ⚠ same type
IAPP p.Leu13Phe Uncertain significance ★ ⚠ same type
IAPP p.Thr23Ile Uncertain significance ★ ⚠ same type

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/iapp-p-asn47ser (accessed [today's date]).

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