Is PDGFRA p.Ala92Pro (c.274G>C) pathogenic?

PDGFRA p.Ala92Pro (c.274G>C) is classified Uncertain significance in PDGFRA (ClinVar, Single submitter, 1 submitter; last evaluated 2026-02-01). AlphaMissense: ambiguous (0.369); Absent from gnomAD v4.1.

How common is PDGFRA p.Ala92Pro (c.274G>C) in the general population?

PDGFRA p.Ala92Pro (c.274G>C) is absent from gnomAD v4.1 (gnomAD).

What do computational predictors say about PDGFRA p.Ala92Pro (c.274G>C)?

AlphaMissense predicts ambiguous (score 0.369) — an in-silico prediction, not a clinical call.

PDGFRA p.Ala92Pro

c.274G>C · VCV4823314

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

ambiguous

0.369 · ACMG-weighted

gnomAD v4.1

Absent

absent from gnomAD v4.1

Computational evidence

Protein change
AlphaMissense	0.369	ambiguous
REVEL	0.313	indeterminate
SaProt	LLR -7.06	tolerated
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 12	GERP 2.1, phastCons 1
Regional constraint	o/e 0.82	unconstrained · MANE · 16 kb · p 1.7e-06 · regional, not allelic
Overall
CADD	24.6	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: PDGFRA
Protein: p.Ala92Pro
Coding: c.274G>C
MANE Select: NM_006206
Type: single nucleotide variant
Location: chr4:54261319 (GRCh38)
Gene constraint: LOEUF 0.264 · pLI 1.00 · ClinGen HI 0/3 (gnomAD)
Structure: AlphaFold pLDDT 72.91 · 19 PDB
Residue 92: the ig-like c2-type 1 domain; an α-helix

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

Similar variants

PDGFRA p.Ala92= Conflicting classifications of pathogenicity ★ same residue
PDGFRA p.Ala92Thr Uncertain significance ★ ⚠ same residue
PDGFRA p.Ala92Val Conflicting classifications of pathogenicity ★ ⚠ same residue
PDGFRA c.1364+3A>G Uncertain significance ★★ same type
PDGFRA c.1364+4T>C Uncertain significance ★★ same type
PDGFRA c.1787-5C>G Uncertain significance ★★ same type
PDGFRA c.2002+2T>C Uncertain significance ★★ same type
PDGFRA c.2002+4G>A Uncertain significance ★★ same type

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-ala92pro (accessed [today's date]).

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