Is PROP1 p.Phe88Ser (c.263T>C) pathogenic?

PROP1 p.Phe88Ser (c.263T>C) is classified Pathogenic in PROP1 (ClinVar, No assertion criteria, 2 submitters; last evaluated 2000-08-01). AlphaMissense: likely pathogenic (0.9824); Absent from gnomAD v4.1; Associated with pituitary hormone deficiency, combined, 2.

What condition is associated with PROP1 p.Phe88Ser (c.263T>C)?

PROP1 p.Phe88Ser (c.263T>C) is associated with pituitary hormone deficiency, combined, 2 (ClinVar).

How common is PROP1 p.Phe88Ser (c.263T>C) in the general population?

PROP1 p.Phe88Ser (c.263T>C) is absent from gnomAD v4.1 (gnomAD).

How is Non-acquired panhypopituitarism inherited?

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

What do computational predictors say about PROP1 p.Phe88Ser (c.263T>C)?

AlphaMissense predicts likely pathogenic (score 0.9824) — an in-silico prediction, not a clinical call.

PROP1 p.Phe88Ser

c.263T>C · rs121917841 · VCV8100

Pathogenic No assertion criteria

Classification

Pathogenic

ClinVar

Review

No assertion criteria ☆☆☆☆

ClinVar · 2 submitters

AlphaMissense

likely pathogenic

0.9824 · ACMG-weighted

gnomAD v4.1

Absent

absent from gnomAD v4.1

Missense predictors

3/3 damaging

AlphaMissense, REVEL, SaProt

Conditions

pituitary hormone deficiency, combined, 2

Computational evidence

Protein change
AlphaMissense	0.9824	likely pathogenic ✓ concordant with ClinVar · top 4% in PROP1
REVEL	0.939	strongly pathogenic-leaning
SaProt	LLR -16.62	damaging
⇒ AlphaMissense, REVEL and SaProt all call this damaging.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 9.9	phastCons 1
Regional constraint	o/e 0.94	unconstrained · MANE · 3,221 bp · p 0.32 · regional, not allelic
Overall
CADD	26.3	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

Absent from gnomAD v4.1. Not observed in any sequenced alleles — a rarity signal (ACMG PM2-supporting), not evidence of pathogenicity on its own.

Variant & gene context

Gene: PROP1
Protein: p.Phe88Ser
Coding: c.263T>C
MANE Select: NM_006261
dbSNP: rs121917841
Type: single nucleotide variant
Location: chr5:177994185 (GRCh38)
Gene constraint: LOEUF 0.87 · pLI 0.01 · ClinGen HI gene assoc. with recessive phenotype (gnomAD)
Structure: AlphaFold pLDDT 70.74
Residue 88: a DNA-binding region; a UniProt-annotated variant site (in cphd2; impairs binding of the mutated protein to dna target sequences)

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 c.109+1G>A Pathogenic ★★ same condition
PROP1 c.110-2A>G Likely pathogenic ★★ same condition
PROP1 c.343-1G>A Likely pathogenic ★★ same condition
PROP1 p.Arg112Ter Pathogenic/Likely pathogenic ★★ same condition
PROP1 p.Arg120Cys Pathogenic/Likely pathogenic ★★ same condition
PROP1 p.Arg125Gln Likely pathogenic ★★ same condition
PROP1 p.Arg125Trp Pathogenic ★★ same condition
PROP1 p.Arg16Ter Pathogenic/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-phe88ser (accessed [today's date]).

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