Is PDGFRA p.Pro267Ser (c.799C>T) pathogenic?

PDGFRA p.Pro267Ser (c.799C>T) is classified Uncertain significance in PDGFRA (ClinVar, Multiple submitters, 4 submitters; last evaluated 2026-01-26). AlphaMissense: ambiguous (0.5212); Very rare (popmax 0.00449%, nfe); Associated with polyps, multiple and recurrent inflammatory fibroid, gastrointestinal.

What condition is associated with PDGFRA p.Pro267Ser (c.799C>T)?

PDGFRA p.Pro267Ser (c.799C>T) is associated with polyps, multiple and recurrent inflammatory fibroid, gastrointestinal, gastrointestinal stromal tumor, hereditary neoplastic syndrome (ClinVar).

How common is PDGFRA p.Pro267Ser (c.799C>T) in the general population?

PDGFRA p.Pro267Ser (c.799C>T) is very rare (popmax 0.00449%, nfe) (gnomAD).

What do computational predictors say about PDGFRA p.Pro267Ser (c.799C>T)?

AlphaMissense predicts ambiguous (score 0.5212) — an in-silico prediction, not a clinical call.

PDGFRA p.Pro267Ser

c.799C>T · rs757378016 · VCV459123

Uncertain significance Multiple submitters

Classification

Uncertain significance

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 4 submitters

AlphaMissense

ambiguous

0.5212 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 0.00449%, nfe)

Missense predictors

0/2 damaging

REVEL, SaProt · AlphaMissense no call

Conditions

polyps, multiple and recurrent inflammatory fibroid, gastrointestinal

Computational evidence

Protein change
AlphaMissense	0.5212	ambiguous
REVEL	0.212	benign-leaning
SaProt	LLR -7.53	tolerated
⇒ REVEL and SaProt both call this tolerated; AlphaMissense makes no call.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 7.5	GERP 2.1, phastCons 1
Regional constraint	o/e 0.82	unconstrained · MANE · 16 kb · p 1.7e-06 · regional, not allelic
Overall
CADD	20.9	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 0.00449% European (non-Finnish) · 53/1,180,016 alleles

Filtering AF 0.0035% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.00318%

Overall 0.00341% 55/1,614,040 alleles · very rare

Ancestry group	Frequency	1 in
European (non-Finnish)grpmax	0.00449%	22,264
Remaining individualsnot grpmax-eligible	0.0032%	31,242

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.Pro267Ser
Coding: c.799C>T
MANE Select: NM_006206
dbSNP: rs757378016
Type: single nucleotide variant
Location: chr4:54267328 (GRCh38)
Gene constraint: LOEUF 0.264 · pLI 1.00 · ClinGen HI 0/3 (gnomAD)
Structure: AlphaFold pLDDT 72.91 · 19 PDB
Residue 267: a β-strand; a disulfide bond; the ig-like c2-type 3 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.Pro267Leu Uncertain significance ★★ ⚠ same residue
PDGFRA p.Pro267= Conflicting classifications of pathogenicity ★ same residue
PDGFRA p.Pro267Thr 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-pro267ser (accessed [today's date]).

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