Is AIP p.Ile327= (c.981C>T) pathogenic?

AIP p.Ile327= (c.981C>T) is classified Likely benign in AIP (ClinVar, Single submitter, 1 submitter; last evaluated 2022-11-15). Very rare (popmax 0.00171%, amr); Associated with hereditary neoplastic syndrome.

What condition is associated with AIP p.Ile327= (c.981C>T)?

AIP p.Ile327= (c.981C>T) is associated with hereditary neoplastic syndrome (ClinVar).

How common is AIP p.Ile327= (c.981C>T) in the general population?

AIP p.Ile327= (c.981C>T) is very rare (popmax 0.00171%, amr) (gnomAD).

AIP p.Ile327=

c.981C>T · rs1049565 · VCV2452480

Likely benign Single submitter

Classification

Likely benign

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

gnomAD v4.1

Rare

very rare (popmax 0.00171%, amr)

Conditions

hereditary neoplastic syndrome

Computational evidence

Protein change
Missense predictors do not apply to this variant type; conservation carries the signal.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 2.7	GERP 0.74, phastCons 1
Overall
CADD	10.56	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.00171% Admixed American · 1/58,506 alleles

Filtering AF 0.000881% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.00072%

Overall 0.00112% 18/1,603,694 alleles · very rare exomes 18/1,451,328 · genomes 0/152,366 · joint denominator

Ancestry group	Frequency	1 in
Admixed Americangrpmax	0.00171%	58,506
European (non-Finnish)	0.00145%	69,164

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.Ile327=
Coding: c.981C>T
MANE Select: NM_003977
dbSNP: rs1049565
Type: single nucleotide variant
Location: chr11:67490981 (GRCh38)
Gene constraint: LOEUF 0.626 · pLI 0.28 (gnomAD)
Structure: AlphaFold pLDDT 91.09 · 5 PDB
Residue 327: 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.Ile327Phe Uncertain significance ★★ ⚠ same residue
AIP p.Ile327Asn 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

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-ile327 (accessed [today's date]).

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