Is AIP p.His330Tyr (c.988C>T) pathogenic?

AIP p.His330Tyr (c.988C>T) is classified Uncertain significance in AIP (ClinVar, Multiple submitters, 2 submitters; last evaluated 2025-08-26). AlphaMissense: likely benign (0.0838); Very rare (popmax 0.000681%, nfe); Associated with hereditary neoplastic syndrome.

What condition is associated with AIP p.His330Tyr (c.988C>T)?

AIP p.His330Tyr (c.988C>T) is associated with hereditary neoplastic syndrome (ClinVar).

How common is AIP p.His330Tyr (c.988C>T) in the general population?

AIP p.His330Tyr (c.988C>T) is very rare (popmax 0.000681%, nfe) (gnomAD).

What do computational predictors say about AIP p.His330Tyr (c.988C>T)?

AlphaMissense predicts likely benign (score 0.0838) — an in-silico prediction, not a clinical call.

AIP p.His330Tyr

c.988C>T · rs2495410801 · VCV2481086

Uncertain significance Multiple submitters

Classification

Uncertain significance

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 2 submitters

AlphaMissense

likely benign

0.0838 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 0.000681%, nfe)

Missense predictors

0/3 damaging

AlphaMissense, REVEL, SaProt

Conditions

hereditary neoplastic syndrome

Computational evidence

Protein change
AlphaMissense	0.0838	likely benign
REVEL	0.219	benign-leaning
SaProt	LLR -8.86	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 4	GERP 0.72, phastCons 1
Overall
CADD	15.1	PHRED · no single calibrated threshold — expert panels disagree

ClinVar classifies this uncertain; the computational predictors unanimously lean tolerated — a triage signal, not a reclassification

AlphaMissense carries the ACMG weight for missense; REVEL and SaProt are independent agreement signals.

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.000681% European (non-Finnish) · 8/1,173,928 alleles

Filtering AF 0.000293% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.000212%

Overall 0.000553% 8/1,447,438 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.His330Tyr
Coding: c.988C>T
MANE Select: NM_017900 · reported on NM_003977
dbSNP: rs2495410801
Type: single nucleotide variant
Location: chr11:67490988 (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.His330= Likely benign ★★ same residue
AIP p.His330Arg 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-his330tyr (accessed [today's date]).

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