Is PDGFRB p.Arg561Cys (c.1681C>T) pathogenic?

PDGFRB p.Arg561Cys (c.1681C>T) is classified Pathogenic in PDGFRB (ClinVar, Multiple submitters, 10 submitters; last evaluated 2025-12-03). AlphaMissense: likely benign (0.3076); Very rare (popmax 8.48e-05%, nfe); Associated with acroosteolysis-keloid-like lesions-premature aging syndrome.

What condition is associated with PDGFRB p.Arg561Cys (c.1681C>T)?

PDGFRB p.Arg561Cys (c.1681C>T) is associated with acroosteolysis-keloid-like lesions-premature aging syndrome, myofibromatosis, infantile, 1, basal ganglia calcification, idiopathic, 4 (ClinVar).

How common is PDGFRB p.Arg561Cys (c.1681C>T) in the general population?

PDGFRB p.Arg561Cys (c.1681C>T) is very rare (popmax 8.48e-05%, nfe) (gnomAD).

What do computational predictors say about PDGFRB p.Arg561Cys (c.1681C>T)?

AlphaMissense predicts likely benign (score 0.3076) — an in-silico prediction, not a clinical call.

PDGFRB p.Arg561Cys

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.1681C>T · rs367543286 · VCV55848

Pathogenic Multiple submitters

Classification

Pathogenic

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 10 submitters

AlphaMissense

likely benign

0.3076 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 8.48e-05%, nfe)

Missense predictors

2/3 damaging

AlphaMissense, REVEL, SaProt

Conditions

acroosteolysis-keloid-like lesions-premature aging syndrome

Computational evidence

Protein change
AlphaMissense	0.3076	likely benign ⚠ discordant with ClinVar
REVEL	0.911	moderately pathogenic-leaning
SaProt	LLR -12.86	damaging
⇒ REVEL and SaProt call this damaging; AlphaMissense does not.
Splicing
SpliceAI	<0.2	all four deltas below 0.2 · G>C here scores Δ0.29 · evaluated, not missing
Constraint at this position
Conservation	phyloP 12	GERP -2.7, phastCons 1
Regional constraint	o/e 0.79	unconstrained · MANE · 16 kb · p 5.4e-12 · regional, not allelic
Overall
CADD	34.0	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 8.48e-05% European (non-Finnish) · 1/1,179,848 alleles

Overall 0.000657% 1/152,176 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.Arg561Cys
Coding: c.1681C>T
MANE Select: NM_002609
dbSNP: rs367543286
Type: single nucleotide variant
Location: chr5:150125571 (GRCh38)
Gene constraint: LOEUF 0.504 · pLI 0.94 (gnomAD)
Structure: AlphaFold pLDDT 72.96 · 9 PDB
Residue 561: a UniProt-annotated variant site (in imf1)

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: myofibromatosis, infantile, 1 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.Arg561_Tyr562delinsHis Pathogenic ★ same residue
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-arg561cys (accessed [today's date]).

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