Is PROP1 p.Ser144Phe (c.431C>T) pathogenic?

PROP1 p.Ser144Phe (c.431C>T) is classified Uncertain significance in PROP1 (ClinVar, Single submitter, 1 submitter; last evaluated 2024-10-08). AlphaMissense: likely benign (0.2305); Very rare (popmax 8.47e-05%, nfe); Associated with Inborn genetic diseases.

What condition is associated with PROP1 p.Ser144Phe (c.431C>T)?

PROP1 p.Ser144Phe (c.431C>T) is associated with Inborn genetic diseases (ClinVar).

How common is PROP1 p.Ser144Phe (c.431C>T) in the general population?

PROP1 p.Ser144Phe (c.431C>T) is very rare (popmax 8.47e-05%, nfe) (gnomAD).

What do computational predictors say about PROP1 p.Ser144Phe (c.431C>T)?

AlphaMissense predicts likely benign (score 0.2305) — an in-silico prediction, not a clinical call.

PROP1 p.Ser144Phe

c.431C>T · VCV3425643

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.2305 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 8.47e-05%, nfe)

Missense predictors

1/2 damaging

AlphaMissense, SaProt · REVEL indeterminate

Conditions

Inborn genetic diseases

Computational evidence

Protein change
AlphaMissense	0.2305	likely benign
REVEL	0.304	indeterminate
SaProt	LLR -10.08	damaging
⇒ SaProt calls this damaging; AlphaMissense does not; REVEL is indeterminate.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 7.4	phastCons 1
Regional constraint	o/e 0.94	unconstrained · MANE · 3,221 bp · p 0.32 · regional, not allelic
Overall
CADD	17.48	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

Grpmax group 8.47e-05% European (non-Finnish) · 1/1,179,978 alleles

Overall 6.2e-05% 1/1,613,994 alleles · very rare exomes 1/1,461,788 · genomes 0/152,206 · 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.Ser144Phe
Coding: c.431C>T
MANE Select: NM_006261
Type: single nucleotide variant
Location: chr5:177992959 (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

Inborn genetic diseases — disease report on Sugi Atlas → Associated genes, phenotypes, clinical trials & treatments

Similar variants

PROP1 p.Arg99Gln Pathogenic/Likely pathogenic ★★ same condition
PROP1 p.Ala186Val Uncertain significance ★★ ⚠ same condition
PROP1 p.Arg104Trp Uncertain significance ★★ ⚠ same condition
PROP1 p.Arg16Gly Uncertain significance ★★ ⚠ same condition
PROP1 p.Arg70His Uncertain significance ★★ ⚠ same condition
PROP1 p.Arg7Cys Uncertain significance ★★ ⚠ same condition
PROP1 p.Gln92His Uncertain significance ★★ same condition
PROP1 p.Gly51Trp Uncertain significance ★★ ⚠ 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-ser144phe (accessed [today's date]).

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