Is PROP1 p.Pro211His (c.632C>A) pathogenic?

PROP1 p.Pro211His (c.632C>A) is classified Uncertain significance in PROP1 (ClinVar, No assertion criteria, 1 submitter; last evaluated 2024-01-25). AlphaMissense: likely benign (0.143); Very rare (popmax 0.00188%, nfe); Associated with PROP1-related disorder.

What condition is associated with PROP1 p.Pro211His (c.632C>A)?

PROP1 p.Pro211His (c.632C>A) is associated with PROP1-related disorder (ClinVar).

How common is PROP1 p.Pro211His (c.632C>A) in the general population?

PROP1 p.Pro211His (c.632C>A) is very rare (popmax 0.00188%, nfe) (gnomAD).

What do computational predictors say about PROP1 p.Pro211His (c.632C>A)?

AlphaMissense predicts likely benign (score 0.143) — an in-silico prediction, not a clinical call.

PROP1 p.Pro211His

c.632C>A · rs775538186 · VCV3047433

Uncertain significance No assertion criteria

Classification

Uncertain significance

ClinVar

Review

No assertion criteria ☆☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.143 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 0.00188%, nfe)

Missense predictors

0/3 damaging

AlphaMissense, REVEL, SaProt

Conditions

PROP1-related disorder

Computational evidence

Protein change
AlphaMissense	0.143	likely benign
REVEL	0.172	moderately benign-leaning
SaProt	LLR -9.22	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 6.2	phastCons 1
Regional constraint	o/e 0.94	unconstrained · MANE · 3,221 bp · p 0.32 · regional, not allelic
Overall
CADD	21.7	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 0.00188% European (non-Finnish) · 22/1,171,430 alleles

Filtering AF 0.00123% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.00105%

Overall 0.00157% 25/1,592,914 alleles · very rare exomes 22/1,441,164 · genomes 3/151,750 · joint denominator

Ancestry group	Frequency	1 in
European (non-Finnish)grpmax	0.00188%	53,247
Finnishnot grpmax-eligible	0.00168%	59,396
Remaining individualsnot grpmax-eligible	0.00162%	61,572
African / African-American	0.00134%	74,498

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.Pro211His
Coding: c.632C>A
MANE Select: NM_006261
dbSNP: rs775538186
Type: single nucleotide variant
Location: chr5:177992758 (GRCh38)
Gene constraint: LOEUF 0.87 · pLI 0.01 · ClinGen HI gene assoc. with recessive phenotype (gnomAD)
Structure: AlphaFold pLDDT 70.74
Residue 211: the 'disordered' region

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

Disease context

PROP1-related disorder

Similar variants

PROP1 p.Pro211= Likely benign ★ same residue
PROP1 p.Arg16Ter Pathogenic/Likely pathogenic ★★ same condition
PROP1 p.Arg99Ter Pathogenic ★★ same condition
PROP1 p.Phe117Ile Pathogenic/Likely pathogenic ★★ same condition
PROP1 p.Pro211fs Likely pathogenic ★★ same residue
PROP1 c.343-11C>G Likely pathogenic ★ same condition
PROP1 p.Leu102fs Pathogenic/Likely pathogenic ★★ same condition
PROP1 c.109+1G>A 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-pro211his (accessed [today's date]).

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