Is RET p.Pro560= (c.1680C>G) pathogenic?

RET p.Pro560= (c.1680C>G) is classified Likely benign in RET (ClinVar, No assertion criteria, 1 submitter; last evaluated 2024-03-09). Absent from gnomAD v4.1; Associated with RET-related disorder.

What condition is associated with RET p.Pro560= (c.1680C>G)?

RET p.Pro560= (c.1680C>G) is associated with RET-related disorder (ClinVar).

How common is RET p.Pro560= (c.1680C>G) in the general population?

RET p.Pro560= (c.1680C>G) is absent from gnomAD v4.1 (gnomAD).

RET p.Pro560=

c.1680C>G · VCV3349076

Likely benign No assertion criteria

Classification

Likely benign

ClinVar

Review

No assertion criteria ☆☆☆☆

ClinVar · 1 submitter

gnomAD v4.1

Absent

absent from gnomAD v4.1

Conditions

RET-related disorder

Computational evidence

Protein change
Missense predictors do not apply to this variant type; conservation carries the signal.
Splicing
SpliceAI	<0.2	all four deltas below 0.2 · C>T here scores Δ0.23 · evaluated, not missing
Constraint at this position
Conservation	phyloP 0.63	GERP -2.4, phastCons 1
Overall
CADD	9.615	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.Pro560=
Coding: c.1680C>G
MANE Select: NM_020975
Type: single nucleotide variant
Location: chr10:43112884 (GRCh38)
Gene constraint: LOEUF 0.24 · pLI 1.00 · ClinGen HI 3/3 (gnomAD)
Structure: AlphaFold pLDDT 79.27 · 34 PDB

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

Disease context

RET-related disorder

Similar variants

RET p.Pro560Ala Uncertain significance ★★ ⚠ same residue
RET p.Pro560Leu Uncertain significance ★ ⚠ same residue
RET p.Pro560Ser Conflicting classifications of pathogenicity ★ ⚠ same residue
RET c.1759+1G>A Pathogenic/Likely pathogenic ★★ same condition
RET p.Arg180Ter Pathogenic ★★ same condition
RET p.Arg897Gln Pathogenic ★★ ⚠ same condition
RET p.Cys609Phe Pathogenic ★★ same condition
RET p.Cys609Tyr 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-pro560 (accessed [today's date]).

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