Is PDGFRB p.Pro427Ser (c.1279C>T) pathogenic?

PDGFRB p.Pro427Ser (c.1279C>T) is classified Benign/Likely benign in PDGFRB (ClinVar, Multiple submitters, 4 submitters; last evaluated 2025-09-08). AlphaMissense: likely benign (0.1118); Rare (popmax 0.144%, amr); Associated with acroosteolysis-keloid-like lesions-premature aging syndrome.

What condition is associated with PDGFRB p.Pro427Ser (c.1279C>T)?

PDGFRB p.Pro427Ser (c.1279C>T) 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.Pro427Ser (c.1279C>T) in the general population?

PDGFRB p.Pro427Ser (c.1279C>T) is rare (popmax 0.144%, amr) (gnomAD).

What do computational predictors say about PDGFRB p.Pro427Ser (c.1279C>T)?

AlphaMissense predicts likely benign (score 0.1118) — an in-silico prediction, not a clinical call.

PDGFRB p.Pro427Ser

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.1279C>T · rs199873101 · VCV766771

Benign/Likely benign Multiple submitters

Classification

Benign/Likely benign

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 4 submitters

AlphaMissense

likely benign

0.1118 · ACMG-weighted

gnomAD v4.1

Rare

rare (popmax 0.144%, amr)

Missense predictors

0/3 damaging

AlphaMissense, REVEL, SaProt

Conditions

acroosteolysis-keloid-like lesions-premature aging syndrome

Computational evidence

Protein change
AlphaMissense	0.1118	likely benign
REVEL	0.168	moderately benign-leaning
SaProt	LLR -4.84	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 9.8	GERP 2, phastCons 1
Regional constraint	o/e 0.79	unconstrained · MANE · 16 kb · p 5.4e-12 · regional, not allelic
Overall
CADD	21.0	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 0.144% Admixed American · 86/59,766 alleles

Filtering AF 0.119% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.11%

Overall 0.00955% 154/1,612,744 alleles · rare

Ancestry group	Frequency	1 in
Admixed Americangrpmax	0.144%	695
Remaining individualsnot grpmax-eligible	0.0192%	5,205
European (non-Finnish)	0.00458%	21,843
African / African-American	0.00267%	37,486

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.Pro427Ser
Coding: c.1279C>T
MANE Select: NM_002609
dbSNP: rs199873101
Type: single nucleotide variant
Location: chr5:150130627 (GRCh38)
Gene constraint: LOEUF 0.504 · pLI 0.94 (gnomAD)
Structure: AlphaFold pLDDT 72.96 · 9 PDB
Residue 427: the ig-like c2-type 5 domain

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-pro427ser (accessed [today's date]).

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