Is AIP p.His120Pro (c.359A>C) pathogenic?

AIP p.His120Pro (c.359A>C) is classified Uncertain significance in AIP (ClinVar, Multiple submitters, 3 submitters; last evaluated 2024-12-23). AlphaMissense: ambiguous (0.5047); Ultra-rare (popmax 0.0111%, eas); Associated with hereditary neoplastic syndrome.

What condition is associated with AIP p.His120Pro (c.359A>C)?

AIP p.His120Pro (c.359A>C) is associated with hereditary neoplastic syndrome (ClinVar).

How common is AIP p.His120Pro (c.359A>C) in the general population?

AIP p.His120Pro (c.359A>C) is ultra-rare (popmax 0.0111%, eas) (gnomAD).

What do computational predictors say about AIP p.His120Pro (c.359A>C)?

AlphaMissense predicts ambiguous (score 0.5047) — an in-silico prediction, not a clinical call.

AIP p.His120Pro

c.359A>C · rs779779725 · VCV1733039

Uncertain significance Multiple submitters

Classification

Uncertain significance

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 3 submitters

AlphaMissense

ambiguous

0.5047 · ACMG-weighted

gnomAD v4.1

Rare

ultra-rare (popmax 0.0111%, eas)

Missense predictors

2/2 damaging

REVEL, SaProt · AlphaMissense no call

Conditions

hereditary neoplastic syndrome

Computational evidence

Protein change
AlphaMissense	0.5047	ambiguous
REVEL	0.936	strongly pathogenic-leaning
SaProt	LLR -13.81	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 11	GERP 0.98, phastCons 1
Overall
CADD	28.9	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 0.0111% East Asian · 5/44,882 alleles

Filtering AF 0.00434% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.00276%

Overall 0.00031% 5/1,612,650 alleles · ultra-rare exomes 5/1,460,338 · genomes 0/152,312 · joint denominator

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.His120Pro
Coding: c.359A>C
MANE Select: NM_003977
dbSNP: rs779779725
Type: single nucleotide variant
Location: chr11:67489346 (GRCh38)
Gene constraint: LOEUF 0.626 · pLI 0.28 (gnomAD)
Structure: AlphaFold pLDDT 91.09 · 5 PDB
Residue 120: the ppiase fkbp-type domain

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.His120Tyr Uncertain significance ★★ ⚠ same residue
AIP p.His120= Likely benign ★★ same residue
AIP p.His120Arg 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

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-his120pro (accessed [today's date]).

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