Is AIP p.Asp45Asn (c.133G>A) pathogenic?

AIP p.Asp45Asn (c.133G>A) is classified Conflicting classifications of pathogenicity in AIP (ClinVar, Conflicting submitters, 3 submitters; last evaluated 2025-06-23). AlphaMissense: likely benign (0.072); Very rare (popmax 0.00666%, afr); Associated with hereditary neoplastic syndrome.

What condition is associated with AIP p.Asp45Asn (c.133G>A)?

AIP p.Asp45Asn (c.133G>A) is associated with hereditary neoplastic syndrome (ClinVar).

How common is AIP p.Asp45Asn (c.133G>A) in the general population?

AIP p.Asp45Asn (c.133G>A) is very rare (popmax 0.00666%, afr) (gnomAD).

What do computational predictors say about AIP p.Asp45Asn (c.133G>A)?

AlphaMissense predicts likely benign (score 0.072) — an in-silico prediction, not a clinical call.

AIP p.Asp45Asn

c.133G>A · rs574205552 · VCV1040600

Conflicting classifications of pathogenicity Conflicting submitters

Classification

Conflicting classifications of pathogenicity

ClinVar

Review

Conflicting submitters ★☆☆☆

ClinVar · 3 submitters

AlphaMissense

likely benign

0.072 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 0.00666%, afr)

Missense predictors

0/3 damaging

AlphaMissense, REVEL, SaProt

Conditions

hereditary neoplastic syndrome

Computational evidence

Protein change
AlphaMissense	0.072	likely benign
REVEL	0.248	benign-leaning
SaProt	LLR -8.25	tolerated
⇒ AlphaMissense, REVEL and SaProt all call this tolerated.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP -1.6	GERP -3.6
Overall
CADD	0.033	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

Grpmax group 0.00666% African / African-American · 5/75,054 alleles

Filtering AF 0.00255% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.00161%

Overall 0.00062% 10/1,614,040 alleles · very rare

Ancestry group	Frequency	1 in
African / African-Americangrpmax	0.00666%	15,011
Admixed American	0.00333%	30,013
Remaining individualsnot grpmax-eligible	0.0016%	62,508
European (non-Finnish)	0.000169%	590,023

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: AIP
Protein: p.Asp45Asn
Coding: c.133G>A
MANE Select: NM_017900 · reported on NM_003977
dbSNP: rs574205552
Type: single nucleotide variant
Location: chr11:67487039 (GRCh38)
Structure: AlphaFold pLDDT 70.14 · 81 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.Asp45Val Uncertain significance ★★ ⚠ 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
AIP p.Gln14Ter Pathogenic ★★ same condition
AIP p.Gln217Ter 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-asp45asn (accessed [today's date]).

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