Is AIP p.Arg191Cys (c.571C>T) pathogenic?

AIP p.Arg191Cys (c.571C>T) is classified Conflicting classifications of pathogenicity in AIP (ClinVar, Conflicting submitters, 5 submitters; last evaluated 2026-02-03). AlphaMissense: likely benign (0.2098); Ultra-rare (popmax 0.049%, eas); Associated with hereditary neoplastic syndrome.

What condition is associated with AIP p.Arg191Cys (c.571C>T)?

AIP p.Arg191Cys (c.571C>T) is associated with hereditary neoplastic syndrome, growth hormone secreting pituitary adenoma 1 (ClinVar).

How common is AIP p.Arg191Cys (c.571C>T) in the general population?

AIP p.Arg191Cys (c.571C>T) is ultra-rare (popmax 0.049%, eas) (gnomAD).

What do computational predictors say about AIP p.Arg191Cys (c.571C>T)?

AlphaMissense predicts likely benign (score 0.2098) — an in-silico prediction, not a clinical call.

AIP p.Arg191Cys

c.571C>T · rs189861025 · VCV825923

Conflicting classifications of pathogenicity Conflicting submitters

Classification

Conflicting classifications of pathogenicity

ClinVar

Review

Conflicting submitters ★☆☆☆

ClinVar · 5 submitters

AlphaMissense

likely benign

0.2098 · ACMG-weighted

gnomAD v4.1

Rare

ultra-rare (popmax 0.049%, eas)

Missense predictors

1/2 damaging

AlphaMissense, SaProt · REVEL no call

Conditions

hereditary neoplastic syndrome

Computational evidence

Protein change
AlphaMissense	0.2098	likely benign
REVEL	0.55	indeterminate
SaProt	LLR -10.46	damaging
⇒ SaProt calls this damaging; AlphaMissense does not; REVEL makes no call.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 3.9	GERP -0.57, phastCons 1
Overall
CADD	28.8	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 0.049% East Asian · 22/44,890 alleles

Filtering AF 0.0331% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.0279%

Overall 0.0018% 29/1,613,360 alleles · ultra-rare

Ancestry group	Frequency	1 in
East Asiangrpmax	0.049%	2,040
African / African-American	0.00267%	37,520
South Asian	0.0022%	45,538
Remaining individualsnot grpmax-eligible	0.0016%	62,500
European (non-Finnish)	0.000169%	589,998

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.Arg191Cys
Coding: c.571C>T
MANE Select: NM_017900 · reported on NM_003977
dbSNP: rs189861025
Type: single nucleotide variant
Location: chr11:67490140 (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

Also linked: growth hormone secreting pituitary adenoma 1

Similar variants

AIP p.Arg191His Uncertain significance ★★ ⚠ same residue
AIP p.Arg191Leu Uncertain significance ★★ ⚠ same residue
AIP p.Arg191= 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

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-arg191cys (accessed [today's date]).

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