Is AIP p.Pro147Thr (c.439C>A) pathogenic?

AIP p.Pro147Thr (c.439C>A) is classified Uncertain significance in AIP (ClinVar, Multiple submitters, 2 submitters; last evaluated 2025-04-11). AlphaMissense: likely benign (0.2385); Absent from gnomAD v4.1; Associated with hereditary neoplastic syndrome.

What condition is associated with AIP p.Pro147Thr (c.439C>A)?

AIP p.Pro147Thr (c.439C>A) is associated with hereditary neoplastic syndrome (ClinVar).

How common is AIP p.Pro147Thr (c.439C>A) in the general population?

AIP p.Pro147Thr (c.439C>A) is absent from gnomAD v4.1 (gnomAD).

What do computational predictors say about AIP p.Pro147Thr (c.439C>A)?

AlphaMissense predicts likely benign (score 0.2385) — an in-silico prediction, not a clinical call.

AIP p.Pro147Thr

c.439C>A · rs2134253545 · VCV2955921

Uncertain significance Multiple submitters

Classification

Uncertain significance

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 2 submitters

AlphaMissense

likely benign

0.2385 · ACMG-weighted

gnomAD v4.1

Absent

absent from gnomAD v4.1

Missense predictors

2/3 damaging

AlphaMissense, REVEL, SaProt

Conditions

hereditary neoplastic syndrome

Computational evidence

Protein change
AlphaMissense	0.2385	likely benign
REVEL	0.818	moderately pathogenic-leaning
SaProt	LLR -12.46	damaging
⇒ REVEL and SaProt call this damaging; AlphaMissense does not.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 3.3	GERP 1.8, phastCons 1
Overall
CADD	24.3	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.Pro147Thr
Coding: c.439C>A
MANE Select: NM_017900 · reported on NM_003977
dbSNP: rs2134253545
Type: single nucleotide variant
Location: chr11:67489426 (GRCh38)
Structure: AlphaFold pLDDT 70.14 · 81 PDB
Residue 147: an α-helix

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.Pro147Leu Uncertain significance ★ ⚠ same residue
AIP p.Pro147fs Pathogenic ★ same residue
AIP p.Pro147Arg Uncertain significance ★ ⚠ same residue
AIP p.Pro147Ser Uncertain significance ★ ⚠ same residue
AIP p.Pro147= Likely benign ★ same residue
AIP p.Arg271Trp Pathogenic/Likely pathogenic ★★ same condition
AIP p.Arg304Ter Pathogenic ★★ same condition
AIP p.Arg81Ter 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-pro147thr (accessed [today's date]).

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