Is PDGFRB p.Pro4= (c.12G>A) pathogenic?

PDGFRB p.Pro4= (c.12G>A) is classified Benign in PDGFRB (ClinVar, Multiple submitters, 3 submitters; last evaluated 2025-12-25). Rare (popmax 0.436%, afr); Associated with skeletal overgrowth-craniofacial dysmorphism-hyperelastic skin-white matter lesions syndrome.

What condition is associated with PDGFRB p.Pro4= (c.12G>A)?

PDGFRB p.Pro4= (c.12G>A) is associated with skeletal overgrowth-craniofacial dysmorphism-hyperelastic skin-white matter lesions syndrome, acroosteolysis-keloid-like lesions-premature aging syndrome, basal ganglia calcification, idiopathic, 4 (ClinVar).

How common is PDGFRB p.Pro4= (c.12G>A) in the general population?

PDGFRB p.Pro4= (c.12G>A) is rare (popmax 0.436%, afr) (gnomAD).

PDGFRB p.Pro4=

c.12G>A · rs138641101 · VCV772769

Benign Multiple submitters

Classification

Benign

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 3 submitters

gnomAD v4.1

Rare

rare (popmax 0.436%, afr)

Conditions

skeletal overgrowth-craniofacial dysmorphism-hyperelastic skin-white matter lesions 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 -0.58	GERP -4.2
Overall
CADD	6.061	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.436% African / African-American · 327/75,032 alleles

Filtering AF 0.397% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.382%

Overall 0.0235% 379/1,613,670 alleles · rare

Ancestry group	Frequency	1 in
African / African-Americangrpmax	0.436%	229
Admixed American	0.0267%	3,749
East Asian	0.0223%	4,485
Remaining individualsnot grpmax-eligible	0.016%	6,250
South Asian	0.00769%	12,998
European (non-Finnish)	0.000763%	131,081

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.Pro4=
Coding: c.12G>A
MANE Select: NM_002609
dbSNP: rs138641101
Type: single nucleotide variant
Location: chr5:150137036 (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

skeletal overgrowth-craniofacial dysmorphism-hyperelastic skin-white matter lesions syndrome — disease report on Sugi Atlas → Associated genes, phenotypes, clinical trials & treatments

Also linked: acroosteolysis-keloid-like lesions-premature aging syndrome basal ganglia calcification, idiopathic, 4 infantile myofibromatosis

Similar variants

PDGFRB p.Pro4Leu Benign ★★ same residue
PDGFRB p.Pro4Gln Conflicting classifications of pathogenicity ★ ⚠ same residue
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

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-pro4 (accessed [today's date]).

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