Is RET p.Tyr809= (c.2427C>T) pathogenic?

RET p.Tyr809= (c.2427C>T) is classified Benign/Likely benign in RET (ClinVar, Multiple submitters, 9 submitters; last evaluated 2026-01-31). Ultra-rare (popmax 0.0366%, mid); Associated with pheochromocytoma.

What condition is associated with RET p.Tyr809= (c.2427C>T)?

RET p.Tyr809= (c.2427C>T) is associated with pheochromocytoma, Hirschsprung disease, susceptibility to, 1, familial medullary thyroid carcinoma (ClinVar).

How common is RET p.Tyr809= (c.2427C>T) in the general population?

RET p.Tyr809= (c.2427C>T) is ultra-rare (popmax 0.0366%, mid) (gnomAD).

RET p.Tyr809=

c.2427C>T · rs577929869 · VCV241347

Benign/Likely benign Multiple submitters

Classification

Benign/Likely benign

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 9 submitters

gnomAD v4.1

Rare

ultra-rare (popmax 0.0366%, mid)

Conditions

pheochromocytoma

Computational evidence

Protein change
Missense predictors do not apply to this variant type; conservation carries the signal.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP -12	GERP -4
Overall
CADD	0.84	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.0366% Middle Eastern · 2/5,460 alleles

Filtering AF 0.00728% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.00516%

Overall 0.00323% 52/1,608,670 alleles · ultra-rare exomes 44/1,456,358 · genomes 8/152,312 · joint denominator

Ancestry group	Frequency	1 in
Middle Easterngrpmax	0.0366%	2,730
East Asian	0.0156%	6,391
Remaining individualsnot grpmax-eligible	0.00804%	12,441
African / African-American	0.004%	24,984
Admixed American	0.00335%	29,858
European (non-Finnish)	0.00263%	38,031
South Asian	0.0022%	45,389

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: RET
Protein: p.Tyr809=
Coding: c.2427C>T
MANE Select: NM_020975
dbSNP: rs577929869
Type: single nucleotide variant
Location: chr10:43119565 (GRCh38)
Gene constraint: LOEUF 0.24 · pLI 1.00 · ClinGen HI 3/3 (gnomAD)
Structure: AlphaFold pLDDT 79.27 · 34 PDB
Residue 809: a modified residue (phosphotyrosine; by autocatalysis); the protein kinase domain

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

Disease context

pheochromocytoma — disease report on Sugi Atlas → Associated genes, phenotypes, clinical trials & treatments

Also linked: Hirschsprung disease, susceptibility to, 1 familial medullary thyroid carcinoma multiple endocrine neoplasia type 2B multiple endocrine neoplasia type 2A hereditary neoplastic syndrome multiple endocrine neoplasia type 2

Similar variants

RET p.Tyr809His Uncertain significance ★★ ⚠ same residue
RET p.Tyr809Ter Pathogenic ★ same residue
RET p.Tyr809Ser Uncertain significance ★ ⚠ same residue
RET c.1759+1G>A Pathogenic/Likely pathogenic ★★ same condition
RET c.1879+1G>A Pathogenic/Likely pathogenic ★★ same condition
RET p.Arg180Ter Pathogenic ★★ same condition
RET p.Arg77Cys Pathogenic/Likely pathogenic ★★ ⚠ same condition
RET p.Arg873Trp Likely 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/ret-p-tyr809 (accessed [today's date]).

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