Is AIP p.His130Pro (c.389A>C) pathogenic?

AIP p.His130Pro (c.389A>C) is classified Uncertain significance in AIP (ClinVar, Multiple submitters, 2 submitters; last evaluated 2025-11-22). AlphaMissense: likely benign (0.1729); Absent from gnomAD v4.1; Associated with hereditary neoplastic syndrome.

What condition is associated with AIP p.His130Pro (c.389A>C)?

AIP p.His130Pro (c.389A>C) is associated with hereditary neoplastic syndrome (ClinVar).

How common is AIP p.His130Pro (c.389A>C) in the general population?

AIP p.His130Pro (c.389A>C) is absent from gnomAD v4.1 (gnomAD).

What do computational predictors say about AIP p.His130Pro (c.389A>C)?

AlphaMissense predicts likely benign (score 0.1729) — an in-silico prediction, not a clinical call.

AIP p.His130Pro

c.389A>C · rs2495401875 · VCV1735967

Uncertain significance Multiple submitters

Classification

Uncertain significance

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 2 submitters

AlphaMissense

likely benign

0.1729 · ACMG-weighted

gnomAD v4.1

Absent

absent from gnomAD v4.1

Missense predictors

1/3 damaging

AlphaMissense, REVEL, SaProt

Conditions

hereditary neoplastic syndrome

Computational evidence

Protein change
AlphaMissense	0.1729	likely benign
REVEL	0.762	pathogenic-leaning
SaProt	LLR -7.42	tolerated
⇒ REVEL calls this damaging; AlphaMissense and SaProt do not.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 9.3	GERP 1, phastCons 1
Overall
CADD	25.1	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: AIP
Protein: p.His130Pro
Coding: c.389A>C
MANE Select: NM_003977
dbSNP: rs2495401875
Type: single nucleotide variant
Location: chr11:67489376 (GRCh38)
Gene constraint: LOEUF 0.626 · pLI 0.28 (gnomAD)
Structure: AlphaFold pLDDT 91.09 · 5 PDB

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

Disease context

hereditary neoplastic syndrome — disease report on Sugi Atlas → Associated genes, phenotypes, clinical trials & treatments

Similar variants

AIP p.His130Asp Uncertain significance ★ ⚠ same residue
AIP p.His130Tyr Uncertain significance ★ ⚠ same residue
AIP p.His130= Likely benign ★ same residue
AIP p.Arg271Trp Pathogenic/Likely pathogenic ★★ same condition
AIP p.Arg304Ter Pathogenic ★★ same condition
AIP p.Arg81Ter Pathogenic ★★ same condition
AIP p.Cys238Tyr Likely pathogenic ★★ same condition
AIP p.Gln126Ter 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/aip-p-his130pro (accessed [today's date]).

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