Is AIP p.Arg307Trp (c.919C>T) pathogenic?

AIP p.Arg307Trp (c.919C>T) is classified Uncertain significance in AIP (ClinVar, Multiple submitters, 3 submitters; last evaluated 2025-10-29). AlphaMissense: likely benign (0.2091); Very rare (popmax 0.005%, amr); Associated with hereditary neoplastic syndrome.

What condition is associated with AIP p.Arg307Trp (c.919C>T)?

AIP p.Arg307Trp (c.919C>T) is associated with hereditary neoplastic syndrome (ClinVar).

How common is AIP p.Arg307Trp (c.919C>T) in the general population?

AIP p.Arg307Trp (c.919C>T) is very rare (popmax 0.005%, amr) (gnomAD).

What do computational predictors say about AIP p.Arg307Trp (c.919C>T)?

AlphaMissense predicts likely benign (score 0.2091) — an in-silico prediction, not a clinical call.

AIP p.Arg307Trp

c.919C>T · rs758248161 · VCV823086

Uncertain significance Multiple submitters

Classification

Uncertain significance

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 3 submitters

AlphaMissense

likely benign

0.2091 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 0.005%, amr)

Missense predictors

1/2 damaging

AlphaMissense, SaProt

Conditions

hereditary neoplastic syndrome

Computational evidence

Protein change
AlphaMissense	0.2091	likely benign
SaProt	LLR -11.48	damaging
⇒ SaProt calls this damaging; AlphaMissense does not.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 1.8	GERP -0.25, phastCons 0.99
Overall
CADD	25.0	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 0.005% Admixed American · 3/59,944 alleles

Filtering AF 0.00133% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.000668%

Overall 0.00093% 15/1,612,382 alleles · very rare

Ancestry group	Frequency	1 in
Admixed Americangrpmax	0.005%	19,981
African / African-American	0.00133%	74,932
South Asian	0.0011%	91,064
European (non-Finnish)	0.000848%	117,987

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.Arg307Trp
Coding: c.919C>T
MANE Select: NM_017900 · reported on NM_003977
dbSNP: rs758248161
Type: single nucleotide variant
Location: chr11:67490919 (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.Arg307= Uncertain significance ★ same residue
AIP p.Arg307Gly Uncertain significance ★ ⚠ same residue
AIP p.Arg307fs Conflicting classifications of pathogenicity ★ same residue
AIP p.Arg307Gln Uncertain significance ★ ⚠ same residue
AIP p.Arg307Pro Uncertain significance ★ ⚠ same residue
AIP p.Arg271Trp Pathogenic/Likely pathogenic ★★ same condition
AIP p.Arg304Ter Pathogenic ★★ same condition
AIP p.Arg81Ter 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-arg307trp (accessed [today's date]).

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