Is PDGFRB p.Arg208Ser (c.624A>C) pathogenic?

PDGFRB p.Arg208Ser (c.624A>C) is classified Likely benign in PDGFRB (ClinVar, Multiple submitters, 2 submitters; last evaluated 2022-03-07). AlphaMissense: likely benign (0.116); Very rare (popmax 0.00619%, nfe); Associated with skeletal overgrowth-craniofacial dysmorphism-hyperelastic skin-white matter lesions syndrome.

What condition is associated with PDGFRB p.Arg208Ser (c.624A>C)?

PDGFRB p.Arg208Ser (c.624A>C) 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.Arg208Ser (c.624A>C) in the general population?

PDGFRB p.Arg208Ser (c.624A>C) is very rare (popmax 0.00619%, nfe) (gnomAD).

What do computational predictors say about PDGFRB p.Arg208Ser (c.624A>C)?

AlphaMissense predicts likely benign (score 0.116) — an in-silico prediction, not a clinical call.

PDGFRB p.Arg208Ser

c.624A>C · rs374440746 · VCV2037288

Likely benign Multiple submitters

Classification

Likely benign

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 2 submitters

AlphaMissense

likely benign

0.116 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 0.00619%, nfe)

Missense predictors

0/3 damaging

AlphaMissense, REVEL, SaProt

Conditions

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

Computational evidence

Protein change
AlphaMissense	0.116	likely benign
REVEL	0.154	moderately benign-leaning
SaProt	LLR -6.10	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 2.6	GERP -2.3, phastCons 1
Regional constraint	o/e 0.79	unconstrained · MANE · 16 kb · p 5.4e-12 · regional, not allelic
Overall
CADD	16.12	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 0.00619% European (non-Finnish) · 73/1,178,646 alleles

Filtering AF 0.00503% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.00463%

Overall 0.00472% 76/1,611,198 alleles · very rare

Ancestry group	Frequency	1 in
European (non-Finnish)grpmax	0.00619%	16,146
Admixed American	0.00167%	59,752
Remaining individualsnot grpmax-eligible	0.0016%	62,386
African / African-American	0.00134%	74,792

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.Arg208Ser
Coding: c.624A>C
MANE Select: NM_002609
dbSNP: rs374440746
Type: single nucleotide variant
Location: chr5:150134757 (GRCh38)
Gene constraint: LOEUF 0.504 · pLI 0.94 (gnomAD)
Structure: AlphaFold pLDDT 72.96 · 9 PDB
Residue 208: a β-strand; the ig-like c2-type 2 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.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-arg208ser (accessed [today's date]).

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