Is PDGFRA p.Pro765Thr (c.2293C>A) pathogenic?

PDGFRA p.Pro765Thr (c.2293C>A) is classified Conflicting classifications of pathogenicity in PDGFRA (ClinVar, Conflicting submitters, 3 submitters; last evaluated 2026-06-15). AlphaMissense: likely pathogenic (0.5683); Very rare (popmax 0.00017%, nfe); Associated with hereditary neoplastic syndrome.

What condition is associated with PDGFRA p.Pro765Thr (c.2293C>A)?

PDGFRA p.Pro765Thr (c.2293C>A) is associated with hereditary neoplastic syndrome, polyps, multiple and recurrent inflammatory fibroid, gastrointestinal, gastrointestinal stromal tumor (ClinVar).

How common is PDGFRA p.Pro765Thr (c.2293C>A) in the general population?

PDGFRA p.Pro765Thr (c.2293C>A) is very rare (popmax 0.00017%, nfe) (gnomAD).

What do computational predictors say about PDGFRA p.Pro765Thr (c.2293C>A)?

AlphaMissense predicts likely pathogenic (score 0.5683) — an in-silico prediction, not a clinical call.

PDGFRA p.Pro765Thr

c.2293C>A · rs1325295795 · VCV961192

Conflicting classifications of pathogenicity Conflicting submitters

Classification

Conflicting classifications of pathogenicity

ClinVar

Review

Conflicting submitters ★☆☆☆

ClinVar · 3 submitters

AlphaMissense

likely pathogenic

0.5683 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 0.00017%, nfe)

Missense predictors

1/2 damaging

AlphaMissense, SaProt · REVEL no call

Conditions

hereditary neoplastic syndrome

Computational evidence

Protein change
AlphaMissense	0.5683	likely pathogenic
REVEL	0.635	indeterminate
SaProt	LLR -7.05	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	26.1	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 0.00017% European (non-Finnish) · 2/1,179,690 alleles

Filtering AF 2.8e-05% ClinGen BA1/BS1 input FAF95, joint · FAF99 1.1e-05%

Overall 0.000137% 2/1,461,428 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.Pro765Thr
Coding: c.2293C>A
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

hereditary neoplastic syndrome — disease report on Sugi Atlas → Associated genes, phenotypes, clinical trials & treatments

Also linked: polyps, multiple and recurrent inflammatory fibroid, gastrointestinal gastrointestinal stromal tumor

Similar variants

PDGFRA p.Pro765= Likely benign ★★ same residue
PDGFRA p.Pro765Gln Uncertain significance ★ ⚠ same residue
PDGFRA p.Pro765Ser 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

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-pro765thr (accessed [today's date]).

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