Is PDGFRB p.Ala6Val (c.17C>T) pathogenic?

PDGFRB p.Ala6Val (c.17C>T) is classified Likely benign in PDGFRB (ClinVar, Multiple submitters, 4 submitters; last evaluated 2025-04-17). AlphaMissense: likely benign (0.0788); Ultra-rare (popmax 0.0589%, nfe); Associated with skeletal overgrowth-craniofacial dysmorphism-hyperelastic skin-white matter lesions syndrome.

What condition is associated with PDGFRB p.Ala6Val (c.17C>T)?

PDGFRB p.Ala6Val (c.17C>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.Ala6Val (c.17C>T) in the general population?

PDGFRB p.Ala6Val (c.17C>T) is ultra-rare (popmax 0.0589%, nfe) (gnomAD).

What do computational predictors say about PDGFRB p.Ala6Val (c.17C>T)?

AlphaMissense predicts likely benign (score 0.0788) — an in-silico prediction, not a clinical call.

PDGFRB p.Ala6Val

c.17C>T · rs150173975 · VCV1586531

Likely benign Multiple submitters

Classification

Likely benign

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 4 submitters

AlphaMissense

likely benign

0.0788 · ACMG-weighted

gnomAD v4.1

Rare

ultra-rare (popmax 0.0589%, 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	0.0788	likely benign
REVEL	0.045	moderately benign-leaning
SaProt	LLR -7.12	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 0.26	GERP -4.2
Regional constraint	o/e 0.79	unconstrained · MANE · 16 kb · p 5.4e-12 · regional, not allelic
Overall
CADD	0.078	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 0.0589% European (non-Finnish) · 695/1,179,580 alleles

Filtering AF 0.0553% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.0538%

Overall 0.0482% 778/1,613,428 alleles · ultra-rare

Ancestry group	Frequency	1 in
European (non-Finnish)grpmax	0.0589%	1,697
Remaining individualsnot grpmax-eligible	0.0576%	1,736
South Asian	0.0253%	3,955
Admixed American	0.015%	6,665
African / African-American	0.0133%	7,504
Ashkenazi Jewishnot grpmax-eligible	0.00676%	14,796
Finnishnot grpmax-eligible	0.00469%	21,328

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.Ala6Val
Coding: c.17C>T
MANE Select: NM_002609
dbSNP: rs150173975
Type: single nucleotide variant
Location: chr5:150137031 (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.Ala6= Likely benign ★★ same residue
PDGFRB p.Ala6Gly 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

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-ala6val (accessed [today's date]).

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