Is AIP p.Glu153Lys (c.457G>A) pathogenic?

AIP p.Glu153Lys (c.457G>A) is classified Uncertain significance in AIP (ClinVar, Multiple submitters, 2 submitters; last evaluated 2023-03-31). AlphaMissense: ambiguous (0.4108); Absent from gnomAD v4.1; Associated with hereditary neoplastic syndrome.

What condition is associated with AIP p.Glu153Lys (c.457G>A)?

AIP p.Glu153Lys (c.457G>A) is associated with hereditary neoplastic syndrome (ClinVar).

How common is AIP p.Glu153Lys (c.457G>A) in the general population?

AIP p.Glu153Lys (c.457G>A) is absent from gnomAD v4.1 (gnomAD).

What do computational predictors say about AIP p.Glu153Lys (c.457G>A)?

AlphaMissense predicts ambiguous (score 0.4108) — an in-silico prediction, not a clinical call.

AIP p.Glu153Lys

c.457G>A · rs376193405 · VCV2566785

Uncertain significance Multiple submitters

Classification

Uncertain significance

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 2 submitters

AlphaMissense

ambiguous

0.4108 · ACMG-weighted

gnomAD v4.1

Absent

absent from gnomAD v4.1

Missense predictors

2/2 damaging

REVEL, SaProt · AlphaMissense no call

Conditions

hereditary neoplastic syndrome

Computational evidence

Protein change
AlphaMissense	0.4108	ambiguous
REVEL	0.847	moderately pathogenic-leaning
SaProt	LLR -11.45	damaging
⇒ REVEL and SaProt both call this damaging; AlphaMissense makes no call.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 9.9	GERP 0.65, phastCons 1
Overall
CADD	27.7	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.Glu153Lys
Coding: c.457G>A
MANE Select: NM_017900 · reported on NM_003977
dbSNP: rs376193405
Type: single nucleotide variant
Location: chr11:67489444 (GRCh38)
Structure: AlphaFold pLDDT 70.14 · 81 PDB
Residue 153: 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.Glu153Asp Uncertain significance ★★ ⚠ same residue
AIP p.Glu153Gly Uncertain significance ★ ⚠ same residue
AIP p.Glu153= 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-glu153lys (accessed [today's date]).

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