Is PDGFRA p.Pro158= (c.474T>C) pathogenic?

PDGFRA p.Pro158= (c.474T>C) is classified Benign/Likely benign in PDGFRA (ClinVar, Multiple submitters, 3 submitters; last evaluated 2026-06-16). Very rare (popmax 0.00167%, amr); Associated with polyps, multiple and recurrent inflammatory fibroid, gastrointestinal.

What condition is associated with PDGFRA p.Pro158= (c.474T>C)?

PDGFRA p.Pro158= (c.474T>C) is associated with polyps, multiple and recurrent inflammatory fibroid, gastrointestinal, gastrointestinal stromal tumor, hereditary neoplastic syndrome (ClinVar).

How common is PDGFRA p.Pro158= (c.474T>C) in the general population?

PDGFRA p.Pro158= (c.474T>C) is very rare (popmax 0.00167%, amr) (gnomAD).

PDGFRA p.Pro158=

c.474T>C · rs1722881178 · VCV1742841

Benign/Likely benign Multiple submitters

Classification

Benign/Likely benign

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 3 submitters

gnomAD v4.1

Rare

very rare (popmax 0.00167%, amr)

Conditions

polyps, multiple and recurrent inflammatory fibroid, gastrointestinal

Computational evidence

Protein change
Missense predictors do not apply to this variant type; conservation carries the signal.
Splicing
SpliceAI	<0.2	all four deltas below 0.2 · T>G here scores Δ0.45 · evaluated, not missing
Constraint at this position
Conservation	phyloP -9.6	GERP -3.6
Overall
CADD	0.065	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.00167% Admixed American · 1/59,986 alleles

Overall 0.000657% 1/152,162 alleles · very rare

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: PDGFRA
Protein: p.Pro158=
Coding: c.474T>C
MANE Select: NM_006206
dbSNP: rs1722881178
Type: single nucleotide variant
Location: chr4:54263773 (GRCh38)
Gene constraint: LOEUF 0.264 · pLI 1.00 · ClinGen HI 0/3 (gnomAD)
Structure: AlphaFold pLDDT 72.91 · 19 PDB
Residue 158: a disulfide bond; the ig-like c2-type 2 domain

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

Disease context

polyps, multiple and recurrent inflammatory fibroid, gastrointestinal — disease report on Sugi Atlas → Associated genes, phenotypes, clinical trials & treatments

Also linked: gastrointestinal stromal tumor hereditary neoplastic syndrome

Similar variants

PDGFRA p.Pro158Ala Uncertain significance ★ ⚠ same residue
PDGFRA c.1364+3A>G Uncertain significance ★★ same condition
PDGFRA c.1364+4T>C Uncertain significance ★★ same condition
PDGFRA c.1787-5C>G Uncertain significance ★★ same condition
PDGFRA c.2002+2T>C Uncertain significance ★★ same condition
PDGFRA c.2002+4G>A Uncertain significance ★★ same condition
PDGFRA c.2002+4G>T Uncertain significance ★★ same condition
PDGFRA c.2002+5G>C 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/pdgfra-p-pro158 (accessed [today's date]).

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