Is RET p.Ala807= (c.2421C>G) pathogenic?

RET p.Ala807= (c.2421C>G) is classified Likely benign in RET (ClinVar, Single submitter, 1 submitter; last evaluated 2022-06-23). Absent from gnomAD v4.1; Associated with hereditary neoplastic syndrome.

What condition is associated with RET p.Ala807= (c.2421C>G)?

RET p.Ala807= (c.2421C>G) is associated with hereditary neoplastic syndrome (ClinVar).

How common is RET p.Ala807= (c.2421C>G) in the general population?

RET p.Ala807= (c.2421C>G) is absent from gnomAD v4.1 (gnomAD).

RET p.Ala807=

c.2421C>G · rs2132943172 · VCV1791025

Likely benign Single submitter

Classification

Likely benign

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

gnomAD v4.1

Absent

absent from gnomAD v4.1

Conditions

hereditary neoplastic syndrome

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 1.8	GERP -0.2, phastCons 1
Overall
CADD	9.485	PHRED · no single calibrated threshold — expert panels disagree

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: RET
Protein: p.Ala807=
Coding: c.2421C>G
MANE Select: NM_020975
dbSNP: rs2132943172
Type: single nucleotide variant
Location: chr10:43119559 (GRCh38)
Gene constraint: LOEUF 0.24 · pLI 1.00 · ClinGen HI 3/3 (gnomAD)
Structure: AlphaFold pLDDT 79.27 · 34 PDB
Residue 807: a UniProt-annotated variant site (confers resistance to vandetanib, lenvatinib and cabozantinib inhibitors); a binding site; the protein kinase domain

Full RET 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

Similar variants

RET p.Ala807Gly Uncertain significance ★★ ⚠ same residue
RET p.Ala807Val Uncertain significance ★★ ⚠ same residue
RET p.Ala807Thr Uncertain significance ★★ ⚠ same residue
RET p.Ala807Ser Uncertain significance ★ ⚠ same residue
RET c.1759+1G>A Pathogenic/Likely pathogenic ★★ same condition
RET p.Arg873Trp Likely pathogenic ★★ same condition
RET p.Asp631Tyr Pathogenic ★★ ⚠ same condition
RET p.Cys609Arg 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-ala807 (accessed [today's date]).

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