Is RET p.Arg587= (c.1759C>A) pathogenic?

RET p.Arg587= (c.1759C>A) is classified Likely benign in RET (ClinVar, Single submitter, 1 submitter; last evaluated 2022-05-13). No allele count reported in gnomAD v4.1 (AN 1,612,774); Associated with hereditary neoplastic syndrome.

What condition is associated with RET p.Arg587= (c.1759C>A)?

RET p.Arg587= (c.1759C>A) is associated with hereditary neoplastic syndrome (ClinVar).

How common is RET p.Arg587= (c.1759C>A) in the general population?

RET p.Arg587= (c.1759C>A) is no allele count reported in gnomAD v4.1 (AN 1,612,774) (gnomAD).

RET p.Arg587=

c.1759C>A · rs748905470 · VCV1779527

Likely benign Single submitter

Classification

Likely benign

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

gnomAD v4.1

Not reported

no allele count reported in gnomAD v4.1 (AN 1,612,774)

Conditions

hereditary neoplastic syndrome

Computational evidence

Protein change
Missense predictors do not apply to this variant type; conservation/SpliceAI carries the signal.
Splicing
SpliceAI	Δ0.23	donor loss, 32 bp away · masked 0 · deltas
Constraint at this position
Conservation	phyloP 1.6	GERP 0.76, phastCons 0.95
Overall
CADD	15.18	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

No allele count reported in gnomAD v4.1 (AN 1,612,774). This is missing data, not an absence: the variant may or may not be present in gnomAD. Rarity (ACMG PM2) and BA1/BS1 cannot be assessed for it.

Variant & gene context

Gene: RET
Protein: p.Arg587=
Coding: c.1759C>A
MANE Select: NM_020975
dbSNP: rs748905470
Type: single nucleotide variant
Location: chr10:43112963 (GRCh38)
Gene constraint: LOEUF 0.24 · pLI 1.00 · ClinGen HI 3/3 (gnomAD)
Structure: AlphaFold pLDDT 79.27 · 34 PDB
Residue 587: a functional site (breakpoint for translocation to form the trim27/ret oncogene)

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.Arg587Trp Uncertain significance ★★ ⚠ same residue
RET p.Arg587Gly 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
RET p.Cys609Gly Pathogenic ★★ same condition
RET p.Cys609Phe 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-arg587 (accessed [today's date]).

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