Is PDGFRA p.Pro765Ser (c.2293C>T) pathogenic?

PDGFRA p.Pro765Ser (c.2293C>T) is classified Uncertain significance in PDGFRA (ClinVar, Single submitter, 1 submitter; last evaluated 2020-03-02). AlphaMissense: likely pathogenic (0.6913); Absent from gnomAD v4.1; Associated with gastrointestinal stromal tumor.

What condition is associated with PDGFRA p.Pro765Ser (c.2293C>T)?

PDGFRA p.Pro765Ser (c.2293C>T) is associated with gastrointestinal stromal tumor (ClinVar).

How common is PDGFRA p.Pro765Ser (c.2293C>T) in the general population?

PDGFRA p.Pro765Ser (c.2293C>T) is absent from gnomAD v4.1 (gnomAD).

How is Gastrointestinal stromal tumor inherited?

Typically Autosomal dominant, Not applicable (Orphanet). A genetic counselor can assess individual risk for a family.

What do computational predictors say about PDGFRA p.Pro765Ser (c.2293C>T)?

AlphaMissense predicts likely pathogenic (score 0.6913) — an in-silico prediction, not a clinical call.

PDGFRA p.Pro765Ser

c.2293C>T · rs1325295795 · VCV1044774

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely pathogenic

0.6913 · ACMG-weighted

gnomAD v4.1

Absent

absent from gnomAD v4.1

Missense predictors

1/2 damaging

AlphaMissense, SaProt · REVEL no call

Conditions

gastrointestinal stromal tumor

Computational evidence

Protein change
AlphaMissense	0.6913	likely pathogenic
REVEL	0.594	indeterminate
SaProt	LLR -6.85	tolerated
⇒ AlphaMissense calls this damaging; SaProt does not; REVEL makes no call.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 7.7	GERP 2.1, phastCons 1
Regional constraint	o/e 0.87	unconstrained · MANE · 7,065 bp · p 0.11 · regional, not allelic
Overall
CADD	26.2	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

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: PDGFRA
Protein: p.Pro765Ser
Coding: c.2293C>T
MANE Select: NM_006206
dbSNP: rs1325295795
Type: single nucleotide variant
Location: chr4:54280452 (GRCh38)
Gene constraint: LOEUF 0.264 · pLI 1.00 · ClinGen HI 0/3 (gnomAD)
Structure: AlphaFold pLDDT 72.91 · 19 PDB
Residue 765: the protein kinase domain

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

Disease context

gastrointestinal stromal tumor — disease report on Sugi Atlas → Associated genes, phenotypes, clinical trials & treatments

For Gastrointestinal stromal tumor (Orphanet):

Inheritance: Autosomal dominant, Not applicable
Onset: Adolescent, Adult, Childhood
Prevalence: 1-5 / 10 000 (Europe)

Similar variants

PDGFRA p.Pro765= Likely benign ★★ same residue
PDGFRA p.Pro765Gln Uncertain significance ★ ⚠ same residue
PDGFRA p.Pro765Thr Conflicting classifications of pathogenicity ★ ⚠ 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

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-pro765ser (accessed [today's date]).

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