Is PROP1 p.Pro32fs (c.95del) pathogenic?

PROP1 p.Pro32fs (c.95del) is classified Pathogenic/Likely pathogenic in PROP1 (ClinVar, Multiple submitters, 2 submitters; last evaluated 2024-05-17). Very rare (popmax 8.47e-05%, nfe); Associated with pituitary hormone deficiency, combined, 2.

What condition is associated with PROP1 p.Pro32fs (c.95del)?

PROP1 p.Pro32fs (c.95del) is associated with pituitary hormone deficiency, combined, 2 (ClinVar).

How common is PROP1 p.Pro32fs (c.95del) in the general population?

PROP1 p.Pro32fs (c.95del) is very rare (popmax 8.47e-05%, nfe) (gnomAD).

How is Non-acquired panhypopituitarism inherited?

Typically Autosomal recessive, X-linked recessive (Orphanet). A genetic counselor can assess individual risk for a family.

PROP1 p.Pro32fs

c.95del · rs2480292680 · VCV2023152

Pathogenic/Likely pathogenic Multiple submitters

Classification

Pathogenic/Likely pathogenic

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 2 submitters

Consequence

frameshift

predicted LoF

gnomAD v4.1

Rare

very rare (popmax 8.47e-05%, nfe)

Conditions

pituitary hormone deficiency, combined, 2

Computational evidence

Protein change
Missense predictors do not apply to this variant type; conservation carries the signal.
Consequence	frameshift	predicted loss-of-function
NMD	predicted	premature termination codon in exon 1 of 3
Splicing
SpliceAI	—	not assessed · substitutions only
Constraint at this position
Conservation	phyloP 2.2	phastCons 0.28

Predicted loss-of-function is descriptive, not an applied PVS1 code.

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 8.47e-05% European (non-Finnish) · 1/1,179,968 alleles

Overall 6.2e-05% 1/1,613,712 alleles · very rare exomes 1/1,461,352 · genomes 0/152,360 · joint denominator

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: PROP1
Protein: p.Pro32fs
Coding: c.95del
MANE Select: NM_006261
dbSNP: rs2480292680
Type: Deletion
Location: chr5:177995839 (GRCh38)
Gene constraint: LOEUF 0.87 · pLI 0.01 · ClinGen HI gene assoc. with recessive phenotype (gnomAD)
Structure: AlphaFold pLDDT 70.74
Residue 32: the 'disordered' region

Full PROP1 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Disease context

pituitary hormone deficiency, combined, 2 — disease report on Sugi Atlas → Associated genes, phenotypes, clinical trials & treatments

For Non-acquired panhypopituitarism (Orphanet):

Inheritance: Autosomal recessive, X-linked recessive
Onset: All ages

Similar variants

PROP1 p.Pro32= Conflicting classifications of pathogenicity ★ same residue
PROP1 p.Arg104fs Pathogenic/Likely pathogenic ★★ same condition
PROP1 p.Gly204fs Likely pathogenic ★★ same condition
PROP1 p.Leu131fs Pathogenic/Likely pathogenic ★★ same condition
PROP1 p.Leu22fs Pathogenic ★★ same condition
PROP1 p.Pro210fs Likely pathogenic ★★ same condition
PROP1 p.Ala186fs Pathogenic ★ same condition
PROP1 p.Gly183fs 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/prop1-p-pro32fs (accessed [today's date]).

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