Is PROP1 p.Val164= (c.492G>A) pathogenic?

PROP1 p.Val164= (c.492G>A) is classified Uncertain significance in PROP1 (ClinVar, No assertion criteria, 1 submitter; last evaluated 2025-03-24). Very rare (popmax 8.48e-05%, nfe); Associated with pituitary hormone deficiency, combined, 2.

What condition is associated with PROP1 p.Val164= (c.492G>A)?

PROP1 p.Val164= (c.492G>A) is associated with pituitary hormone deficiency, combined, 2 (ClinVar).

How common is PROP1 p.Val164= (c.492G>A) in the general population?

PROP1 p.Val164= (c.492G>A) is very rare (popmax 8.48e-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.Val164=

c.492G>A · VCV4060504

Uncertain significance No assertion criteria

Classification

Uncertain significance

ClinVar

Review

No assertion criteria ☆☆☆☆

ClinVar · 1 submitter

gnomAD v4.1

Rare

very rare (popmax 8.48e-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.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP -0.27
Overall
CADD	2.687	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 8.48e-05% European (non-Finnish) · 1/1,179,920 alleles

Overall 6.2e-05% 1/1,613,660 alleles · very rare exomes 1/1,461,686 · genomes 0/151,974 · 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.Val164=
Coding: c.492G>A
MANE Select: NM_006261
Type: single nucleotide variant
Location: chr5:177992898 (GRCh38)
Gene constraint: LOEUF 0.87 · pLI 0.01 · ClinGen HI gene assoc. with recessive phenotype (gnomAD)
Structure: AlphaFold pLDDT 70.74

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-val164 (accessed [today's date]).

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