Is PDGFRB p.Val125Met (c.373G>A) pathogenic?

PDGFRB p.Val125Met (c.373G>A) is classified Conflicting classifications of pathogenicity in PDGFRB (ClinVar, Conflicting submitters, 2 submitters; last evaluated 2024-10-11). AlphaMissense: likely benign (0.074); Ultra-rare (popmax 0.0203%, mid); Associated with Inborn genetic diseases.

What condition is associated with PDGFRB p.Val125Met (c.373G>A)?

PDGFRB p.Val125Met (c.373G>A) is associated with Inborn genetic diseases, acroosteolysis-keloid-like lesions-premature aging syndrome, basal ganglia calcification, idiopathic, 4 (ClinVar).

How common is PDGFRB p.Val125Met (c.373G>A) in the general population?

PDGFRB p.Val125Met (c.373G>A) is ultra-rare (popmax 0.0203%, mid) (gnomAD).

What do computational predictors say about PDGFRB p.Val125Met (c.373G>A)?

AlphaMissense predicts likely benign (score 0.074) — an in-silico prediction, not a clinical call.

PDGFRB p.Val125Met

c.373G>A · rs540587683 · VCV2949487

Conflicting classifications of pathogenicity Conflicting submitters

Classification

Conflicting classifications of pathogenicity

ClinVar

Review

Conflicting submitters ★☆☆☆

ClinVar · 2 submitters

AlphaMissense

likely benign

0.074 · ACMG-weighted

gnomAD v4.1

Rare

ultra-rare (popmax 0.0203%, mid)

Missense predictors

0/3 damaging

AlphaMissense, REVEL, SaProt

Conditions

Inborn genetic diseases

Computational evidence

Protein change
AlphaMissense	0.074	likely benign
REVEL	0.013	strongly benign-leaning
SaProt	LLR -6.74	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 -1.1	GERP -3.9
Regional constraint	o/e 0.79	unconstrained · MANE · 16 kb · p 5.4e-12 · regional, not allelic
Overall
CADD	0.296	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 0.0203% Middle Eastern · 1/4,926 alleles

Filtering AF 0.0073% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.00555%

Overall 0.00243% 38/1,565,848 alleles · ultra-rare exomes 30/1,413,528 · genomes 8/152,320 · joint denominator

Ancestry group	Frequency	1 in
Middle Easterngrpmax	0.0203%	4,926
African / African-American	0.0135%	7,409
Remaining individualsnot grpmax-eligible	0.00988%	10,119
Ashkenazi Jewishnot grpmax-eligible	0.00697%	14,352
East Asian	0.00225%	44,532
Admixed American	0.00169%	59,284
European (non-Finnish)	0.00149%	67,097

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.Val125Met
Coding: c.373G>A
MANE Select: NM_002609
dbSNP: rs540587683
Type: single nucleotide variant
Location: chr5:150135008 (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

Inborn genetic diseases — 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 skeletal overgrowth-craniofacial dysmorphism-hyperelastic skin-white matter lesions syndrome infantile myofibromatosis

Similar variants

PDGFRB p.Val125Leu Likely benign ★ 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-val125met (accessed [today's date]).

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