Is PDGFRA p.Ser29Pro (c.85T>C) pathogenic?

PDGFRA p.Ser29Pro (c.85T>C) is classified Conflicting classifications of pathogenicity in PDGFRA (ClinVar, Conflicting submitters, 2 submitters; last evaluated 2025-04-14). AlphaMissense: ambiguous (0.4973); Very rare (popmax 0.00329%, sas); Associated with hereditary neoplastic syndrome.

What condition is associated with PDGFRA p.Ser29Pro (c.85T>C)?

PDGFRA p.Ser29Pro (c.85T>C) is associated with hereditary neoplastic syndrome, gastrointestinal stromal tumor (ClinVar).

How common is PDGFRA p.Ser29Pro (c.85T>C) in the general population?

PDGFRA p.Ser29Pro (c.85T>C) is very rare (popmax 0.00329%, sas) (gnomAD).

What do computational predictors say about PDGFRA p.Ser29Pro (c.85T>C)?

AlphaMissense predicts ambiguous (score 0.4973) — an in-silico prediction, not a clinical call.

PDGFRA p.Ser29Pro

c.85T>C · rs746846673 · VCV939895

Conflicting classifications of pathogenicity Conflicting submitters

Classification

Conflicting classifications of pathogenicity

ClinVar

Review

Conflicting submitters ★☆☆☆

ClinVar · 2 submitters

AlphaMissense

ambiguous

0.4973 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 0.00329%, sas)

Missense predictors

1/2 damaging

REVEL, SaProt · AlphaMissense no call

Conditions

hereditary neoplastic syndrome

Computational evidence

Protein change
AlphaMissense	0.4973	ambiguous
REVEL	0.101	moderately benign-leaning
SaProt	LLR -10.18	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 0.27	GERP -1.8, phastCons 0.99
Regional constraint	o/e 0.82	unconstrained · MANE · 16 kb · p 1.7e-06 · regional, not allelic
Overall
CADD	15.71	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 0.00329% South Asian · 3/91,082 alleles

Filtering AF 0.000875% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.000443%

Overall 0.000205% 3/1,461,848 alleles · very rare

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: PDGFRA
Protein: p.Ser29Pro
Coding: c.85T>C
MANE Select: NM_006206
dbSNP: rs746846673
Type: single nucleotide variant
Location: chr4:54261130 (GRCh38)
Gene constraint: LOEUF 0.264 · pLI 1.00 · ClinGen HI 0/3 (gnomAD)
Structure: AlphaFold pLDDT 72.91 · 19 PDB
Residue 29: the ig-like c2-type 1 domain; a β-strand

Full PDGFRA gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Disease context

hereditary neoplastic syndrome — disease report on Sugi Atlas → Associated genes, phenotypes, clinical trials & treatments

Also linked: gastrointestinal stromal tumor

Similar variants

PDGFRA p.Ser29Phe Uncertain significance ★★ ⚠ same residue
PDGFRA p.Ser29Ala Uncertain significance ★ ⚠ same residue
PDGFRA c.1364+3A>G Uncertain significance ★★ same condition
PDGFRA c.1364+4T>C Uncertain significance ★★ same condition
PDGFRA c.1787-5C>G Uncertain significance ★★ same condition
PDGFRA c.2002+2T>C Uncertain significance ★★ same condition
PDGFRA c.2002+4G>A Uncertain significance ★★ same condition
PDGFRA c.2002+4G>T 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/pdgfra-p-ser29pro (accessed [today's date]).

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