Is PDGFRB p.Arg511Cys (c.1531C>T) pathogenic?

PDGFRB p.Arg511Cys (c.1531C>T) is classified Uncertain significance in PDGFRB (ClinVar, Single submitter, 1 submitter; last evaluated 2023-05-15). AlphaMissense: likely benign (0.1505); Very rare (popmax 0.00801%, afr); Associated with skeletal overgrowth-craniofacial dysmorphism-hyperelastic skin-white matter lesions syndrome.

What condition is associated with PDGFRB p.Arg511Cys (c.1531C>T)?

PDGFRB p.Arg511Cys (c.1531C>T) 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.Arg511Cys (c.1531C>T) in the general population?

PDGFRB p.Arg511Cys (c.1531C>T) is very rare (popmax 0.00801%, afr) (gnomAD).

What do computational predictors say about PDGFRB p.Arg511Cys (c.1531C>T)?

AlphaMissense predicts likely benign (score 0.1505) — an in-silico prediction, not a clinical call.

PDGFRB p.Arg511Cys

c.1531C>T · rs765383598 · VCV2929326

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.1505 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 0.00801%, afr)

Missense predictors

1/3 damaging

AlphaMissense, REVEL, SaProt

Conditions

skeletal overgrowth-craniofacial dysmorphism-hyperelastic skin-white matter lesions syndrome

Computational evidence

Protein change
AlphaMissense	0.1505	likely benign
REVEL	0.269	benign-leaning
SaProt	LLR -10.72	damaging
⇒ SaProt calls this damaging; AlphaMissense and REVEL do not.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 3.8	GERP 2.1, phastCons 0.98
Regional constraint	o/e 0.79	unconstrained · MANE · 16 kb · p 5.4e-12 · regional, not allelic
Overall
CADD	24.2	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 0.00801% African / African-American · 6/74,942 alleles

Filtering AF 0.00347% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.00228%

Overall 0.00118% 19/1,613,816 alleles · very rare

Ancestry group	Frequency	1 in
African / African-Americangrpmax	0.00801%	12,490
East Asian	0.00445%	22,453
Remaining individualsnot grpmax-eligible	0.0032%	31,240
South Asian	0.0022%	45,544
European (non-Finnish)	0.000593%	168,573

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.Arg511Cys
Coding: c.1531C>T
MANE Select: NM_002609
dbSNP: rs765383598
Type: single nucleotide variant
Location: chr5:150129805 (GRCh38)
Gene constraint: LOEUF 0.504 · pLI 0.94 (gnomAD)
Structure: AlphaFold pLDDT 72.96 · 9 PDB
Residue 511: the ig-like c2-type 5 domain

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.Arg511His Uncertain significance ★ ⚠ 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
PDGFRB p.Trp566Arg 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-arg511cys (accessed [today's date]).

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