Is PDGFRA p.Ala7Val (c.20C>T) pathogenic?

PDGFRA p.Ala7Val (c.20C>T) is classified Conflicting classifications of pathogenicity in PDGFRA (ClinVar, Conflicting submitters, 3 submitters; last evaluated 2026-06-12). AlphaMissense: likely benign (0.0863); Very rare (popmax 0.00223%, eas); Associated with polyps, multiple and recurrent inflammatory fibroid, gastrointestinal.

What condition is associated with PDGFRA p.Ala7Val (c.20C>T)?

PDGFRA p.Ala7Val (c.20C>T) is associated with polyps, multiple and recurrent inflammatory fibroid, gastrointestinal, gastrointestinal stromal tumor, hereditary neoplastic syndrome (ClinVar).

How common is PDGFRA p.Ala7Val (c.20C>T) in the general population?

PDGFRA p.Ala7Val (c.20C>T) is very rare (popmax 0.00223%, eas) (gnomAD).

What do computational predictors say about PDGFRA p.Ala7Val (c.20C>T)?

AlphaMissense predicts likely benign (score 0.0863) — an in-silico prediction, not a clinical call.

PDGFRA p.Ala7Val

c.20C>T · rs764472307 · VCV240325

Conflicting classifications of pathogenicity Conflicting submitters

Classification

Conflicting classifications of pathogenicity

ClinVar

Review

Conflicting submitters ★☆☆☆

ClinVar · 3 submitters

AlphaMissense

likely benign

0.0863 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 0.00223%, eas)

Missense predictors

0/3 damaging

AlphaMissense, REVEL, SaProt

Conditions

polyps, multiple and recurrent inflammatory fibroid, gastrointestinal

Computational evidence

Protein change
AlphaMissense	0.0863	likely benign
REVEL	0.05	moderately benign-leaning
SaProt	LLR -5.68	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 -0.12	GERP -3.4
Regional constraint	o/e 0.82	unconstrained · MANE · 16 kb · p 1.7e-06 · regional, not allelic
Overall
CADD	9.205	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 0.00223% East Asian · 1/44,882 alleles

Filtering AF 0.000429% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.000313%

Overall 0.000821% 12/1,461,170 alleles · very rare

Ancestry group	Frequency	1 in
East Asiangrpmax	0.00223%	44,882
Admixed American	0.00167%	60,022
European (non-Finnish)	0.000848%	117,938

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.Ala7Val
Coding: c.20C>T
MANE Select: NM_006206
dbSNP: rs764472307
Type: single nucleotide variant
Location: chr4:54258788 (GRCh38)
Gene constraint: LOEUF 0.264 · pLI 1.00 · ClinGen HI 0/3 (gnomAD)
Structure: AlphaFold pLDDT 72.91 · 19 PDB

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

Disease context

polyps, multiple and recurrent inflammatory fibroid, gastrointestinal — disease report on Sugi Atlas → Associated genes, phenotypes, clinical trials & treatments

Also linked: gastrointestinal stromal tumor hereditary neoplastic syndrome

Similar variants

PDGFRA p.Ala7Ser Uncertain significance ★★ ⚠ same residue
PDGFRA p.Ala7= Benign/Likely benign ★★ same residue
PDGFRA p.Ala7Glu Conflicting classifications of pathogenicity ★ ⚠ same residue
PDGFRA p.Ala7Pro 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

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-ala7val (accessed [today's date]).

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