Is PDGFRB p.Ala342Val (c.1025C>T) pathogenic?

PDGFRB p.Ala342Val (c.1025C>T) is classified Likely pathogenic in PDGFRB (ClinVar, Single submitter, 1 submitter; last evaluated 2020-05-05). AlphaMissense: likely pathogenic (0.8186); Absent from gnomAD v4.1; Associated with skeletal overgrowth-craniofacial dysmorphism-hyperelastic skin-white matter lesions syndrome.

How common is PDGFRB p.Ala342Val (c.1025C>T) in the general population?

PDGFRB p.Ala342Val (c.1025C>T) is absent from gnomAD v4.1 (gnomAD).

What do computational predictors say about PDGFRB p.Ala342Val (c.1025C>T)?

AlphaMissense predicts likely pathogenic (score 0.8186) — an in-silico prediction, not a clinical call.

PDGFRB p.Ala342Val

Q: What condition is associated with PDGFRB p.Ala342Val (c.1025C>T)?

PDGFRB p.Ala342Val (c.1025C>T) is associated with skeletal overgrowth-craniofacial dysmorphism-hyperelastic skin-white matter lesions syndrome (ClinVar).

c.1025C>T · rs2113907045 · VCV1333888

Likely pathogenic Single submitter

Classification

Likely pathogenic

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely pathogenic

0.8186 · ACMG-weighted

gnomAD v4.1

Absent

absent from gnomAD v4.1

Missense predictors

1/2 damaging

AlphaMissense, SaProt · REVEL no call

Conditions

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

Computational evidence

Protein change
AlphaMissense	0.8186	likely pathogenic ✓ concordant with ClinVar
REVEL	0.399	indeterminate
SaProt	LLR -9.92	tolerated
⇒ AlphaMissense calls this damaging; SaProt does not; REVEL makes no call.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 12	GERP 2.2, phastCons 1
Regional constraint	o/e 0.79	unconstrained · MANE · 16 kb · p 5.4e-12 · regional, not allelic
Overall
CADD	26.7	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

Absent from gnomAD v4.1. Not observed in any sequenced alleles — a rarity signal (ACMG PM2-supporting), not evidence of pathogenicity on its own.

Variant & gene context

Gene: PDGFRB
Protein: p.Ala342Val
Coding: c.1025C>T
MANE Select: NM_002609
dbSNP: rs2113907045
Type: single nucleotide variant
Location: chr5:150132852 (GRCh38)
Gene constraint: LOEUF 0.504 · pLI 0.94 (gnomAD)
Structure: AlphaFold pLDDT 72.96 · 9 PDB
Residue 342: the ig-like c2-type 4 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

Similar variants

PDGFRB p.Arg561Cys Pathogenic ★★ ⚠ same condition
PDGFRB p.Asn666His 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
PDGFRB p.Ala828Val Uncertain significance ★★ ⚠ same condition
PDGFRB p.Arg113Trp 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-ala342val (accessed [today's date]).

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