Is PDGFRA p.Val69Ala (c.206T>C) pathogenic?

PDGFRA p.Val69Ala (c.206T>C) is classified Conflicting classifications of pathogenicity in PDGFRA (ClinVar, Conflicting submitters, 3 submitters; last evaluated 2026-01-09). AlphaMissense: likely benign (0.1986); Ultra-rare (popmax 0.0231%, sas); Associated with gastrointestinal stromal tumor.

What condition is associated with PDGFRA p.Val69Ala (c.206T>C)?

PDGFRA p.Val69Ala (c.206T>C) is associated with gastrointestinal stromal tumor, polyps, multiple and recurrent inflammatory fibroid, gastrointestinal, hereditary neoplastic syndrome (ClinVar).

How common is PDGFRA p.Val69Ala (c.206T>C) in the general population?

PDGFRA p.Val69Ala (c.206T>C) is ultra-rare (popmax 0.0231%, sas) (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.Val69Ala (c.206T>C)?

AlphaMissense predicts likely benign (score 0.1986) — an in-silico prediction, not a clinical call.

PDGFRA p.Val69Ala

c.206T>C · rs757101121 · VCV843187

Conflicting classifications of pathogenicity Conflicting submitters

Classification

Conflicting classifications of pathogenicity

ClinVar

Review

Conflicting submitters ★☆☆☆

ClinVar · 3 submitters

AlphaMissense

likely benign

0.1986 · ACMG-weighted

gnomAD v4.1

Rare

ultra-rare (popmax 0.0231%, sas)

Missense predictors

0/3 damaging

AlphaMissense, REVEL, SaProt

Conditions

gastrointestinal stromal tumor

Computational evidence

Protein change
AlphaMissense	0.1986	likely benign
REVEL	0.104	moderately benign-leaning
SaProt	LLR -9.40	tolerated
⇒ AlphaMissense, REVEL and SaProt all call this tolerated.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 7.9	GERP 2.1, phastCons 1
Regional constraint	o/e 0.82	unconstrained · MANE · 16 kb · p 1.7e-06 · regional, not allelic
Overall
CADD	20.2	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

Grpmax group 0.0231% South Asian · 21/91,074 alleles

Filtering AF 0.0154% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.0129%

Overall 0.00142% 23/1,614,114 alleles · ultra-rare

Ancestry group	Frequency	1 in
South Asiangrpmax	0.0231%	4,337
Remaining individualsnot grpmax-eligible	0.0032%	31,254

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.Val69Ala
Coding: c.206T>C
MANE Select: NM_006206
dbSNP: rs757101121
Type: single nucleotide variant
Location: chr4:54261251 (GRCh38)
Gene constraint: LOEUF 0.264 · pLI 1.00 · ClinGen HI 0/3 (gnomAD)
Structure: AlphaFold pLDDT 72.91 · 19 PDB
Residue 69: a disulfide bond; the ig-like c2-type 1 domain; a β-strand

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

Also linked: polyps, multiple and recurrent inflammatory fibroid, gastrointestinal hereditary neoplastic syndrome

For Gastrointestinal stromal tumor (Orphanet):

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

Similar variants

PDGFRA p.Val69Glu Uncertain significance ★ ⚠ same residue
PDGFRA p.Val69Met Uncertain significance ★ ⚠ same residue
PDGFRA p.Val69= Likely benign ★ 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-val69ala (accessed [today's date]).

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