Is AIP p.Asp172= (c.516C>T) pathogenic?

AIP p.Asp172= (c.516C>T) is classified Benign/Likely benign in AIP (ClinVar, Multiple submitters, 9 submitters; last evaluated 2026-02-04). Common (popmax 15.3%, eas) — too common for a highly-penetrant pathogenic allele; Associated with hereditary neoplastic syndrome.

What condition is associated with AIP p.Asp172= (c.516C>T)?

AIP p.Asp172= (c.516C>T) is associated with hereditary neoplastic syndrome, growth hormone secreting pituitary adenoma 1 (ClinVar).

AIP p.Asp172=

Q: How common is AIP p.Asp172= (c.516C>T) in the general population?

AIP p.Asp172= (c.516C>T) is common (popmax 15.3%, eas) — too common for a highly-penetrant pathogenic allele (gnomAD).

c.516C>T · rs2276020 · VCV305728

Benign/Likely benign Multiple submitters

Classification

Benign/Likely benign

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 9 submitters

gnomAD v4.1

Common

common (popmax 15.3%, eas) — too common for a highly-penetrant pathogenic allele

Conditions

hereditary neoplastic syndrome

Computational evidence

Protein change
Missense predictors do not apply to this variant type; conservation carries the signal.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP -6.8	GERP -3.3
Overall
CADD	4.052	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 15.3% East Asian · 6,853/44,800 alleles

Filtering AF 15% ClinGen BA1/BS1 input FAF95, joint · FAF99 14.9%

Overall 2.2% 35,497/1,611,554 alleles · common exomes 30,542/1,459,286 · genomes 4,955/152,268 · joint denominator

Ancestry group	Frequency	1 in
East Asiangrpmax	15.3%	7
Finnishnot grpmax-eligible	6.24%	16
African / African-American	4.63%	22
South Asian	3.6%	28
Ashkenazi Jewishnot grpmax-eligible	2.78%	36
Remaining individualsnot grpmax-eligible	2.68%	37
Admixed American	2.6%	38
Middle Eastern	1.39%	72
European (non-Finnish)	1.17%	85

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.Asp172=
Coding: c.516C>T
MANE Select: NM_003977
dbSNP: rs2276020
Type: single nucleotide variant
Location: chr11:67490085 (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

Also linked: growth hormone secreting pituitary adenoma 1

Similar variants

AIP p.Asp172fs Pathogenic ★ same residue
AIP p.Asp172_Glu173del 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-asp172 (accessed [today's date]).

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