Is PROP1 p.Ser19Arg (c.57C>G) pathogenic?

PROP1 p.Ser19Arg (c.57C>G) is classified Uncertain significance in PROP1 (ClinVar, Single submitter, 1 submitter; last evaluated 2021-11-14). AlphaMissense: likely benign (0.1547); Absent from gnomAD v4.1.

How common is PROP1 p.Ser19Arg (c.57C>G) in the general population?

PROP1 p.Ser19Arg (c.57C>G) is absent from gnomAD v4.1 (gnomAD).

What do computational predictors say about PROP1 p.Ser19Arg (c.57C>G)?

AlphaMissense predicts likely benign (score 0.1547) — an in-silico prediction, not a clinical call.

PROP1 p.Ser19Arg

c.57C>G · rs1755756418 · VCV1476836

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.1547 · ACMG-weighted

gnomAD v4.1

Absent

absent from gnomAD v4.1

Missense predictors

0/3 damaging

AlphaMissense, REVEL, SaProt

Computational evidence

Protein change
AlphaMissense	0.1547	likely benign
REVEL	0.169	moderately benign-leaning
SaProt	LLR -5.92	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 0.21
Regional constraint	o/e 0.94	unconstrained · MANE · 3,221 bp · p 0.32 · regional, not allelic
Overall
CADD	11.41	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

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.Ser19Arg
Coding: c.57C>G
MANE Select: NM_006261
dbSNP: rs1755756418
Type: single nucleotide variant
Location: chr5:177995877 (GRCh38)
Gene constraint: LOEUF 0.87 · pLI 0.01 · ClinGen HI gene assoc. with recessive phenotype (gnomAD)
Structure: AlphaFold pLDDT 70.74
Residue 19: the 'disordered' region

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

Similar variants

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
PROP1 p.Arg16Ter Pathogenic/Likely 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-ser19arg (accessed [today's date]).

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