Is PDGFRA p.Ala92= (c.276G>A) pathogenic?

PDGFRA p.Ala92= (c.276G>A) is classified Conflicting classifications of pathogenicity in PDGFRA (ClinVar, Conflicting submitters, 7 submitters; last evaluated 2026-06-16). Ultra-rare (popmax 0.0661%, nfe); Associated with polyps, multiple and recurrent inflammatory fibroid, gastrointestinal.

What condition is associated with PDGFRA p.Ala92= (c.276G>A)?

PDGFRA p.Ala92= (c.276G>A) is associated with polyps, multiple and recurrent inflammatory fibroid, gastrointestinal, gastrointestinal stromal tumor, idiopathic hypereosinophilic syndrome (ClinVar).

How common is PDGFRA p.Ala92= (c.276G>A) in the general population?

PDGFRA p.Ala92= (c.276G>A) is ultra-rare (popmax 0.0661%, nfe) (gnomAD).

PDGFRA p.Ala92=

c.276G>A · rs140725151 · VCV240335

Conflicting classifications of pathogenicity Conflicting submitters

Classification

Conflicting classifications of pathogenicity

ClinVar

Review

Conflicting submitters ★☆☆☆

ClinVar · 7 submitters

gnomAD v4.1

Rare

ultra-rare (popmax 0.0661%, nfe)

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	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP -6	GERP -4.3
Overall
CADD	1.283	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.0661% European (non-Finnish) · 780/1,179,986 alleles

Filtering AF 0.0622% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.0607%

Overall 0.0502% 811/1,613,984 alleles · ultra-rare exomes 768/1,461,840 · genomes 43/152,144 · joint denominator

Ancestry group	Frequency	1 in
European (non-Finnish)grpmax	0.0661%	1,513
African / African-American	0.0213%	4,685
Remaining individualsnot grpmax-eligible	0.0192%	5,209
Admixed American	0.005%	20,000

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.Ala92=
Coding: c.276G>A
MANE Select: NM_006206
dbSNP: rs140725151
Type: single nucleotide variant
Location: chr4:54261321 (GRCh38)
Gene constraint: LOEUF 0.264 · pLI 1.00 · ClinGen HI 0/3 (gnomAD)
Structure: AlphaFold pLDDT 72.91 · 19 PDB
Residue 92: the ig-like c2-type 1 domain; an α-helix

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 idiopathic hypereosinophilic syndrome hereditary neoplastic syndrome

Similar variants

PDGFRA p.Ala92Val Conflicting classifications of pathogenicity ★ ⚠ same residue
PDGFRA p.Ala92Pro Uncertain significance ★ same residue
PDGFRA p.Ala92Thr 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-ala92 (accessed [today's date]).

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