Is RET p.Pro668Val (c.2001_2003inv) pathogenic?

RET p.Pro668Val (c.20012003inv) is classified Uncertain significance in RET (ClinVar, Single submitter, 1 submitter; last evaluated 2026-01-08). Associated with hereditary neoplastic syndrome.

What condition is associated with RET p.Pro668Val (c.2001_2003inv)?

RET p.Pro668Val (c.2001_2003inv) is associated with hereditary neoplastic syndrome (ClinVar).

RET p.Pro668Val

c.2001_2003inv · VCV4844014

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

gnomAD v4.1

Rare

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 · substitutions only
Constraint at this position
Conservation	phyloP -7.4	GERP -3.7
Regional constraint	o/e 0.88	unconstrained · MANE · 17 kb · p 0.00012 · regional, not allelic

Variant & gene context

Gene: RET
Protein: p.Pro668Val
Coding: c.2001_2003inv
MANE Select: NM_020975
Type: Inversion
Location: chr10:43114601 (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

hereditary neoplastic syndrome — disease report on Sugi Atlas → Associated genes, phenotypes, clinical trials & treatments

Similar variants

RET p.Pro668Leu Uncertain significance ★★ ⚠ same residue
RET p.Pro668Ala Uncertain significance ★ ⚠ same residue
RET p.Pro668Ser Uncertain significance ★ ⚠ same residue
RET p.Pro668= Conflicting classifications of pathogenicity ★ same residue
RET p.Tyr1062Ile Uncertain significance ★ same condition
RET c.1759+1G>A Pathogenic/Likely pathogenic ★★ same condition
RET c.1760-2_1760-1del Likely pathogenic ★★ same condition
RET p.Ala883Phe Pathogenic/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-pro668val (accessed [today's date]).

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