Is AIP p.Ser220Phe (c.659C>T) pathogenic?

AIP p.Ser220Phe (c.659C>T) is classified Uncertain significance in AIP (ClinVar, Multiple submitters, 2 submitters; last evaluated 2024-08-06). AlphaMissense: ambiguous (0.4162); No allele count reported in gnomAD v4.1 (AN 1,612,550); Associated with hereditary neoplastic syndrome.

What condition is associated with AIP p.Ser220Phe (c.659C>T)?

AIP p.Ser220Phe (c.659C>T) is associated with hereditary neoplastic syndrome (ClinVar).

How common is AIP p.Ser220Phe (c.659C>T) in the general population?

AIP p.Ser220Phe (c.659C>T) is no allele count reported in gnomAD v4.1 (AN 1,612,550) (gnomAD).

What do computational predictors say about AIP p.Ser220Phe (c.659C>T)?

AlphaMissense predicts ambiguous (score 0.4162) — an in-silico prediction, not a clinical call.

AIP p.Ser220Phe

c.659C>T · rs1488470719 · VCV1025098

Uncertain significance Multiple submitters

Classification

Uncertain significance

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 2 submitters

AlphaMissense

ambiguous

0.4162 · ACMG-weighted

gnomAD v4.1

Not reported

no allele count reported in gnomAD v4.1 (AN 1,612,550)

Conditions

hereditary neoplastic syndrome

Computational evidence

Protein change
AlphaMissense	0.4162	ambiguous
REVEL	0.444	indeterminate
SaProt	LLR -9.54	tolerated
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 4.9	GERP 0.68, phastCons 1
Overall
CADD	26.6	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

No allele count reported in gnomAD v4.1 (AN 1,612,550). This is missing data, not an absence: the variant may or may not be present in gnomAD. Rarity (ACMG PM2) and BA1/BS1 cannot be assessed for it.

Variant & gene context

Gene: AIP
Protein: p.Ser220Phe
Coding: c.659C>T
MANE Select: NM_003977
dbSNP: rs1488470719
Type: single nucleotide variant
Location: chr11:67490329 (GRCh38)
Gene constraint: LOEUF 0.626 · pLI 0.28 (gnomAD)
Structure: AlphaFold pLDDT 91.09 · 5 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.Ser220Tyr Uncertain significance ★ ⚠ same residue
AIP p.Ser220= 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

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-ser220phe (accessed [today's date]).

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