Is AIP p.Thr40Met (c.119C>T) pathogenic?

AIP p.Thr40Met (c.119C>T) is classified Uncertain significance in AIP (ClinVar, Multiple submitters, 3 submitters; last evaluated 2026-02-27). AlphaMissense: ambiguous (0.5167); Very rare (popmax 0.00271%, nfe); Associated with hereditary neoplastic syndrome.

What condition is associated with AIP p.Thr40Met (c.119C>T)?

AIP p.Thr40Met (c.119C>T) is associated with hereditary neoplastic syndrome (ClinVar).

How common is AIP p.Thr40Met (c.119C>T) in the general population?

AIP p.Thr40Met (c.119C>T) is very rare (popmax 0.00271%, nfe) (gnomAD).

What do computational predictors say about AIP p.Thr40Met (c.119C>T)?

AlphaMissense predicts ambiguous (score 0.5167) — an in-silico prediction, not a clinical call.

AIP p.Thr40Met

c.119C>T · rs142044984 · VCV818567

Uncertain significance Multiple submitters

Classification

Uncertain significance

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 3 submitters

AlphaMissense

ambiguous

0.5167 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 0.00271%, nfe)

Missense predictors

2/2 damaging

REVEL, SaProt · AlphaMissense no call

Conditions

hereditary neoplastic syndrome

Computational evidence

Protein change
AlphaMissense	0.5167	ambiguous
REVEL	0.863	moderately pathogenic-leaning
SaProt	LLR -10.30	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 7.6	GERP 1.6, phastCons 1
Overall
CADD	31.0	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 0.00271% European (non-Finnish) · 32/1,180,058 alleles

Filtering AF 0.00196% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.00168%

Overall 0.00217% 35/1,613,906 alleles · very rare

Ancestry group	Frequency	1 in
European (non-Finnish)grpmax	0.00271%	36,877
East Asian	0.00223%	44,890
Remaining individualsnot grpmax-eligible	0.0016%	62,486
African / African-American	0.00133%	74,914

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.Thr40Met
Coding: c.119C>T
MANE Select: NM_017900 · reported on NM_003977
dbSNP: rs142044984
Type: single nucleotide variant
Location: chr11:67487025 (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.Thr40= 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
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-thr40met (accessed [today's date]).

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