Is AIP p.Ala207Thr (c.619G>A) pathogenic?

AIP p.Ala207Thr (c.619G>A) is classified Conflicting classifications of pathogenicity in AIP (ClinVar, Conflicting submitters, 3 submitters; last evaluated 2025-04-27). AlphaMissense: ambiguous (0.5547); Ultra-rare (popmax 0.0187%, sas); Associated with hereditary neoplastic syndrome.

What condition is associated with AIP p.Ala207Thr (c.619G>A)?

AIP p.Ala207Thr (c.619G>A) is associated with hereditary neoplastic syndrome (ClinVar).

How common is AIP p.Ala207Thr (c.619G>A) in the general population?

AIP p.Ala207Thr (c.619G>A) is ultra-rare (popmax 0.0187%, sas) (gnomAD).

What do computational predictors say about AIP p.Ala207Thr (c.619G>A)?

AlphaMissense predicts ambiguous (score 0.5547) — an in-silico prediction, not a clinical call.

AIP p.Ala207Thr

c.619G>A · rs1323279729 · VCV485073

Conflicting classifications of pathogenicity Conflicting submitters

Classification

Conflicting classifications of pathogenicity

ClinVar

Review

Conflicting submitters ★☆☆☆

ClinVar · 3 submitters

AlphaMissense

ambiguous

0.5547 · ACMG-weighted

gnomAD v4.1

Rare

ultra-rare (popmax 0.0187%, sas)

Missense predictors

0/2 damaging

REVEL, SaProt · AlphaMissense no call

Conditions

hereditary neoplastic syndrome

Computational evidence

Protein change
AlphaMissense	0.5547	ambiguous
REVEL	0.188	benign-leaning
SaProt	LLR -4.21	tolerated
⇒ REVEL and SaProt both call this tolerated; AlphaMissense makes no call.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 12	GERP -0.57, phastCons 1
Overall
CADD	24.8	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 0.0187% South Asian · 17/91,078 alleles

Filtering AF 0.0118% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.00976%

Overall 0.0013% 19/1,460,968 alleles · ultra-rare

Ancestry group	Frequency	1 in
South Asiangrpmax	0.0187%	5,358
Middle Eastern	0.0165%	6,062
European (non-Finnish)	8.47e-05%	1,179,988

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.Ala207Thr
Coding: c.619G>A
MANE Select: NM_017900 · reported on NM_003977
dbSNP: rs1323279729
Type: single nucleotide variant
Location: chr11:67490188 (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.Ala207Val Uncertain significance ★★ ⚠ same residue
AIP p.Ala207Gly Uncertain significance ★ ⚠ same residue
AIP p.Ala207Pro Uncertain significance ★ ⚠ same residue
AIP p.Ala207= 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

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-ala207thr (accessed [today's date]).

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