Is RET p.Ser1094= (c.3282T>C) pathogenic?

RET p.Ser1094= (c.3282T>C) is classified Likely benign in RET (ClinVar, Multiple submitters, 3 submitters; last evaluated 2025-11-06). Very rare (popmax 0.0011%, sas); Associated with multiple endocrine neoplasia type 2.

What condition is associated with RET p.Ser1094= (c.3282T>C)?

RET p.Ser1094= (c.3282T>C) is associated with multiple endocrine neoplasia type 2, hereditary neoplastic syndrome (ClinVar).

How common is RET p.Ser1094= (c.3282T>C) in the general population?

RET p.Ser1094= (c.3282T>C) is very rare (popmax 0.0011%, sas) (gnomAD).

How is Multiple endocrine neoplasia type 2 inherited?

Typically Autosomal dominant (Orphanet). A genetic counselor can assess individual risk for a family.

RET p.Ser1094=

c.3282T>C · rs779779706 · VCV2889747

Likely benign Multiple submitters

Classification

Likely benign

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 3 submitters

gnomAD v4.1

Rare

very rare (popmax 0.0011%, sas)

Conditions

multiple endocrine neoplasia type 2

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 4.3	GERP 0.83, phastCons 1
Overall
CADD	10.0	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.0011% South Asian · 1/91,086 alleles

Overall 6.2e-05% 1/1,614,190 alleles · very rare exomes 1/1,461,874 · genomes 0/152,316 · joint denominator

Rarity supports pathogenicity (ACMG PM2); frequency above a disease-specific BA1/BS1 threshold argues against it. A variant frequent in one ancestry group can be near-absent in others, so a single global figure can mislead.

Variant & gene context

Gene: RET
Protein: p.Ser1094=
Coding: c.3282T>C
MANE Select: NM_020975
dbSNP: rs779779706
Type: single nucleotide variant
Location: chr10:43128206 (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

multiple endocrine neoplasia type 2 — disease report on Sugi Atlas → Associated genes, phenotypes, clinical trials & treatments

Also linked: hereditary neoplastic syndrome

For Multiple endocrine neoplasia type 2 (Orphanet):

Inheritance: Autosomal dominant
Onset: Adolescent, Adult, Childhood, Infancy
Prevalence: 1-9 / 100 000 (Europe)

Similar variants

RET p.Ser1094Arg Uncertain significance ★★ ⚠ same residue
RET p.Ser1094Asn Uncertain significance ★★ ⚠ same residue
RET p.Ser1094Gly Uncertain significance ★★ ⚠ same residue
RET p.Ser1094Ile Uncertain significance ★ ⚠ same residue
RET p.Ser1094fs Uncertain significance ★ same residue
RET c.1759+1G>A Pathogenic/Likely pathogenic ★★ same condition
RET c.1879+1G>A Pathogenic/Likely pathogenic ★★ same condition
RET p.Arg180Ter 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-ser1094 (accessed [today's date]).

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