Is RET p.Ser148del (c.443_445del) pathogenic?

RET p.Ser148del (c.443445del) is classified Conflicting classifications of pathogenicity in RET (ClinVar, Conflicting submitters, 5 submitters; last evaluated 2026-04-29). No gnomAD frequency available for this variant; Associated with multiple endocrine neoplasia type 2.

What condition is associated with RET p.Ser148del (c.443_445del)?

RET p.Ser148del (c.443_445del) is associated with multiple endocrine neoplasia type 2, hereditary neoplastic syndrome (ClinVar).

How common is RET p.Ser148del (c.443_445del) in the general population?

RET p.Ser148del (c.443_445del) is no gnomAD frequency available for this variant (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.Ser148del

c.443_445del · rs2492157382 · VCV2916120

Conflicting classifications of pathogenicity Conflicting submitters

Classification

Conflicting classifications of pathogenicity

ClinVar

Review

Conflicting submitters ★☆☆☆

ClinVar · 5 submitters

gnomAD v4.1

Not reported

no gnomAD frequency available for this variant

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 · substitutions only
Constraint at this position
Conservation	phyloP 7.8	GERP 1.7, phastCons 1

Population frequency

dbSNP / gnomAD

No gnomAD frequency available for this variant. 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.Ser148del
Coding: c.443_445del
MANE Select: NM_020975
dbSNP: rs2492157382
Type: Deletion
Location: chr10:43102445 (GRCh38)
Gene constraint: LOEUF 0.24 · pLI 1.00 · ClinGen HI 3/3 (gnomAD)
Structure: AlphaFold pLDDT 79.27 · 34 PDB
Residue 148: a β-strand; the 'cadherin-like region 1 (cld1)' region

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.Ser148Phe Uncertain significance ★★ ⚠ same residue
RET p.Ser148= Conflicting classifications of pathogenicity ★ same residue
RET c.1760-2_1760-1del Likely pathogenic ★★ same condition
RET p.Glu337fs Pathogenic/Likely pathogenic ★★ same condition
RET c.1264-3del Uncertain significance ★★ same condition
RET c.867+4del Uncertain significance ★★ same condition
RET p.Glu818_Gly825del Uncertain significance ★★ same condition
RET p.Ser1021del 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-ser148del (accessed [today's date]).

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