Is PDGFRB p.Glu975= (c.2925G>A) pathogenic?

PDGFRB p.Glu975= (c.2925G>A) is classified Likely benign in PDGFRB (ClinVar, Single submitter, 1 submitter; last evaluated 2024-07-23). Very rare (popmax 0.00167%, amr); Associated with acroosteolysis-keloid-like lesions-premature aging syndrome.

What condition is associated with PDGFRB p.Glu975= (c.2925G>A)?

PDGFRB p.Glu975= (c.2925G>A) is associated with acroosteolysis-keloid-like lesions-premature aging syndrome, basal ganglia calcification, idiopathic, 4, skeletal overgrowth-craniofacial dysmorphism-hyperelastic skin-white matter lesions syndrome (ClinVar).

How common is PDGFRB p.Glu975= (c.2925G>A) in the general population?

PDGFRB p.Glu975= (c.2925G>A) is very rare (popmax 0.00167%, amr) (gnomAD).

PDGFRB p.Glu975=

Q: How is Acroosteolysis-keloid-like lesions-premature aging syndrome inherited?

Typically Autosomal dominant (Orphanet). A genetic counselor can assess individual risk for a family.

c.2925G>A · VCV3763890

Likely benign Single submitter

Classification

Likely benign

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

gnomAD v4.1

Rare

very rare (popmax 0.00167%, amr)

Conditions

acroosteolysis-keloid-like lesions-premature aging syndrome

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 0.59	GERP 2, phastCons 1
Overall
CADD	9.434	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.00167% Admixed American · 1/59,792 alleles

Overall 0.000657% 1/152,152 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: PDGFRB
Protein: p.Glu975=
Coding: c.2925G>A
MANE Select: NM_002609
Type: single nucleotide variant
Location: chr5:150117830 (GRCh38)
Gene constraint: LOEUF 0.504 · pLI 0.94 (gnomAD)
Structure: AlphaFold pLDDT 72.96 · 9 PDB

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

Disease context

acroosteolysis-keloid-like lesions-premature aging syndrome — disease report on Sugi Atlas → Associated genes, phenotypes, clinical trials & treatments

Also linked: basal ganglia calcification, idiopathic, 4 skeletal overgrowth-craniofacial dysmorphism-hyperelastic skin-white matter lesions syndrome infantile myofibromatosis

For Acroosteolysis-keloid-like lesions-premature aging syndrome (Orphanet):

Inheritance: Autosomal dominant
Onset: Infancy, Neonatal

Similar variants

PDGFRB p.Arg561Cys Pathogenic ★★ ⚠ same condition
PDGFRB p.Asn666His Pathogenic/Likely pathogenic ★★ same condition
PDGFRB p.Asn666Lys Pathogenic/Likely pathogenic ★★ same condition
PDGFRB p.Asn666Ser Pathogenic/Likely pathogenic ★★ same condition
PDGFRB p.Pro560Leu Pathogenic/Likely pathogenic ★★ same condition
PDGFRB p.Pro584Arg Pathogenic ★★ same condition
PDGFRB p.Trp566Arg Pathogenic ★★ same condition
PDGFRB p.Ala513Thr 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/pdgfrb-p-glu975 (accessed [today's date]).

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