Is RET p.Val282fs (c.840_843dup) pathogenic?

RET p.Val282fs (c.840843dup) is classified Pathogenic in RET (ClinVar, Single submitter, 1 submitter; last evaluated 2025-05-07). Associated with hereditary neoplastic syndrome.

What condition is associated with RET p.Val282fs (c.840_843dup)?

RET p.Val282fs (c.840_843dup) is associated with hereditary neoplastic syndrome (ClinVar).

RET p.Val282fs

c.840_843dup · VCV3944686

Pathogenic Single submitter

Classification

Pathogenic

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

Consequence

frameshift

predicted LoF

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.
Consequence	frameshift	predicted loss-of-function in a haploinsufficient gene (ClinGen)
NMD	predicted	premature termination codon in exon 4 of 20
Splicing
SpliceAI	—	not assessed · substitutions only
Constraint at this position
Conservation	phyloP 0.95	GERP -0.31, phastCons 0.013

Predicted loss-of-function is descriptive, not an applied PVS1 code.

Variant & gene context

Gene: RET
Protein: p.Val282fs
Coding: c.840_843dup
MANE Select: NM_020975
Type: Duplication
Location: chr10:43105165 (GRCh38)
Gene constraint: LOEUF 0.24 · pLI 1.00 · ClinGen HI 3/3 (gnomAD)
Structure: AlphaFold pLDDT 79.27 · 34 PDB
Residue 282: the 'cadherin-like region 3 (cld3)' region

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.Val282Met Uncertain significance ★★ ⚠ same residue
RET p.Val282= Likely benign ★★ same residue
RET p.Val282Ala Uncertain significance ★ ⚠ same residue
RET p.Val282Gly Uncertain significance ★ ⚠ same residue
RET c.3027_3039+19dup Uncertain significance ★★ same condition
RET p.Arg177_Glu178insIleArg Uncertain significance ★★ same condition
RET p.Cys630_Asp631insProLeuCys Uncertain significance ★★ same condition
RET p.Leu17_Leu18insArgLeuLeuLeuLeuLeu Uncertain significance ★★ 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-val282fs (accessed [today's date]).

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