Is AIP p.Ile18Thr (c.53T>C) pathogenic?

AIP p.Ile18Thr (c.53T>C) is classified Uncertain significance in AIP (ClinVar, Multiple submitters, 3 submitters; last evaluated 2024-10-11). AlphaMissense: likely benign (0.2648); Very rare (popmax 0.000339%, nfe); Associated with hereditary neoplastic syndrome.

What condition is associated with AIP p.Ile18Thr (c.53T>C)?

AIP p.Ile18Thr (c.53T>C) is associated with hereditary neoplastic syndrome (ClinVar).

How common is AIP p.Ile18Thr (c.53T>C) in the general population?

AIP p.Ile18Thr (c.53T>C) is very rare (popmax 0.000339%, nfe) (gnomAD).

What do computational predictors say about AIP p.Ile18Thr (c.53T>C)?

AlphaMissense predicts likely benign (score 0.2648) — an in-silico prediction, not a clinical call.

AIP p.Ile18Thr

c.53T>C · rs773224238 · VCV825703

Uncertain significance Multiple submitters

Classification

Uncertain significance

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 3 submitters

AlphaMissense

likely benign

0.2648 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 0.000339%, nfe)

Missense predictors

1/2 damaging

AlphaMissense, SaProt · REVEL no call

Conditions

hereditary neoplastic syndrome

Computational evidence

Protein change
AlphaMissense	0.2648	likely benign
REVEL	0.596	indeterminate
SaProt	LLR -10.33	damaging
⇒ SaProt calls this damaging; AlphaMissense does not; REVEL makes no call.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 7.8	GERP 2, phastCons 1
Overall
CADD	23.0	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 0.000339% European (non-Finnish) · 4/1,179,994 alleles

Filtering AF 7.9e-05% ClinGen BA1/BS1 input FAF95, joint · FAF99 5.4e-05%

Overall 0.000274% 4/1,461,852 alleles · very rare

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.Ile18Thr
Coding: c.53T>C
MANE Select: NM_003977
dbSNP: rs773224238
Type: single nucleotide variant
Location: chr11:67483211 (GRCh38)
Gene constraint: LOEUF 0.626 · pLI 0.28 (gnomAD)
Structure: AlphaFold pLDDT 91.09 · 5 PDB
Residue 18: a β-strand

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.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
AIP p.Trp168Ter 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-ile18thr (accessed [today's date]).

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