Is PROP1 p.Pro78Ser (c.232C>T) pathogenic?

PROP1 p.Pro78Ser (c.232C>T) is classified Uncertain significance in PROP1 (ClinVar, Single submitter, 1 submitter; last evaluated 2024-02-17). AlphaMissense: likely benign (0.1168); Very rare (popmax 0.00133%, afr).

How common is PROP1 p.Pro78Ser (c.232C>T) in the general population?

PROP1 p.Pro78Ser (c.232C>T) is very rare (popmax 0.00133%, afr) (gnomAD).

What do computational predictors say about PROP1 p.Pro78Ser (c.232C>T)?

AlphaMissense predicts likely benign (score 0.1168) — an in-silico prediction, not a clinical call.

PROP1 p.Pro78Ser

c.232C>T · rs949519377 · VCV1471289

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.1168 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 0.00133%, afr)

Missense predictors

0/3 damaging

AlphaMissense, REVEL, SaProt

Computational evidence

Protein change
AlphaMissense	0.1168	likely benign
REVEL	0.272	benign-leaning
SaProt	LLR -6.85	tolerated
⇒ AlphaMissense, REVEL and SaProt all call this tolerated.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 4.8	phastCons 1
Regional constraint	o/e 0.94	unconstrained · MANE · 3,221 bp · p 0.32 · regional, not allelic
Overall
CADD	11.79	PHRED · no single calibrated threshold — expert panels disagree

ClinVar classifies this uncertain; the computational predictors unanimously lean tolerated — a triage signal, not a reclassification

AlphaMissense carries the ACMG weight for missense; REVEL and SaProt are independent agreement signals.

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.00133% African / African-American · 1/74,914 alleles

Overall 6.2e-05% 1/1,614,028 alleles · very rare exomes 0/1,461,858 · genomes 1/152,170 · 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.Pro78Ser
Coding: c.232C>T
MANE Select: NM_006261
dbSNP: rs949519377
Type: single nucleotide variant
Location: chr5:177994216 (GRCh38)
Gene constraint: LOEUF 0.87 · pLI 0.01 · ClinGen HI gene assoc. with recessive phenotype (gnomAD)
Structure: AlphaFold pLDDT 70.74
Residue 78: a DNA-binding region

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

Similar variants

PROP1 p.Pro78= Conflicting classifications of pathogenicity ★ same residue
PROP1 c.109+1G>A Pathogenic ★★ same type
PROP1 c.110-2A>G Likely pathogenic ★★ same type
PROP1 c.343-1G>A Likely pathogenic ★★ same type
PROP1 p.Arg112Ter Pathogenic/Likely pathogenic ★★ same type
PROP1 p.Arg120Cys Pathogenic/Likely pathogenic ★★ same type
PROP1 p.Arg125Gln Likely pathogenic ★★ same type
PROP1 p.Arg125Trp Pathogenic ★★ same type

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-pro78ser (accessed [today's date]).

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