Is PDGFB p.Arg142Cys (c.424C>T) pathogenic?

PDGFB p.Arg142Cys (c.424C>T) is classified Uncertain significance in PDGFB (ClinVar, Multiple submitters, 2 submitters; last evaluated 2023-10-16). AlphaMissense: ambiguous (0.3498); Ultra-rare (popmax 0.015%, sas); Associated with Inborn genetic diseases.

What condition is associated with PDGFB p.Arg142Cys (c.424C>T)?

PDGFB p.Arg142Cys (c.424C>T) is associated with Inborn genetic diseases (ClinVar).

How common is PDGFB p.Arg142Cys (c.424C>T) in the general population?

PDGFB p.Arg142Cys (c.424C>T) is ultra-rare (popmax 0.015%, sas) (gnomAD).

What do computational predictors say about PDGFB p.Arg142Cys (c.424C>T)?

AlphaMissense predicts ambiguous (score 0.3498) — an in-silico prediction, not a clinical call.

PDGFB p.Arg142Cys

c.424C>T · rs758929255 · VCV3210824

Uncertain significance Multiple submitters

Classification

Uncertain significance

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 2 submitters

AlphaMissense

ambiguous

0.3498 · ACMG-weighted

gnomAD v4.1

Rare

ultra-rare (popmax 0.015%, sas)

Missense predictors

1/2 damaging

REVEL, SaProt · AlphaMissense no call

Conditions

Inborn genetic diseases

Computational evidence

Protein change
AlphaMissense	0.3498	ambiguous
REVEL	0.234	benign-leaning
SaProt	LLR -11.07	damaging
⇒ SaProt calls this damaging; REVEL does not; AlphaMissense makes no call.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 7.2	GERP -0.93, phastCons 1
Regional constraint	o/e 0.87	unconstrained · MANE · 18 kb · p 0.021 · regional, not allelic
Overall
CADD	31.0	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 0.015% South Asian · 13/86,814 alleles

Filtering AF 0.00883% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.00701%

Overall 0.00126% 20/1,582,820 alleles · ultra-rare

Ancestry group	Frequency	1 in
South Asiangrpmax	0.015%	6,678
African / African-American	0.00269%	37,172
Admixed American	0.0018%	55,522
European (non-Finnish)	0.000343%	291,396

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: PDGFB
Protein: p.Arg142Cys
Coding: c.424C>T
MANE Select: NM_002608
dbSNP: rs758929255
Type: single nucleotide variant
Location: chr22:39231654 (GRCh38)
Gene constraint: LOEUF 0.473 · pLI 0.99 (gnomAD)
Structure: AlphaFold pLDDT 73.77 · 6 PDB
Residue 142: a disulfide bond; a β-strand

Full PDGFB 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

Similar variants

PDGFB p.Ala6Val Uncertain significance ★★ ⚠ same condition
PDGFB p.Arg160Trp Uncertain significance ★★ ⚠ same condition
PDGFB p.Arg187Gln Uncertain significance ★★ ⚠ same condition
PDGFB p.Arg187Trp Uncertain significance ★★ ⚠ same condition
PDGFB p.Arg207Gln Uncertain significance ★★ ⚠ same condition
PDGFB p.Arg214Gln Uncertain significance ★★ ⚠ same condition
PDGFB p.Arg46Cys Uncertain significance ★★ ⚠ same condition
PDGFB p.Gln199His 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/pdgfb-p-arg142cys (accessed [today's date]).

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