Is RET p.Ala883Phe (c.2647_2648delinsTT) pathogenic?

RET p.Ala883Phe (c.26472648delinsTT) is classified Pathogenic/Likely pathogenic in RET (ClinVar, Multiple submitters, 4 submitters; last evaluated 2024-06-02). Absent from gnomAD; Associated with hereditary neoplastic syndrome.

What condition is associated with RET p.Ala883Phe (c.2647_2648delinsTT)?

RET p.Ala883Phe (c.2647_2648delinsTT) is associated with hereditary neoplastic syndrome, multiple endocrine neoplasia type 2B, multiple endocrine neoplasia type 2 (ClinVar).

How common is RET p.Ala883Phe (c.2647_2648delinsTT) in the general population?

RET p.Ala883Phe (c.2647_2648delinsTT) is absent from gnomAD (gnomAD).

RET p.Ala883Phe

c.2647_2648delinsTT · rs377767429 · VCV38629

Pathogenic/Likely pathogenic Multiple submitters

Classification

Pathogenic/Likely pathogenic

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 4 submitters

gnomAD v4.1

Not reported

no gnomAD frequency available for this variant

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 12	GERP -0.12, phastCons 1
Regional constraint	o/e 0.47	unconstrained · MANE · 4,087 bp · p 2.5e-11 · regional, not allelic

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.Ala883Phe
Coding: c.2647_2648delinsTT
MANE Select: NM_020975
dbSNP: rs377767429
Type: Indel
Location: chr10:43120120 (GRCh38)
Gene constraint: LOEUF 0.24 · pLI 1.00 · ClinGen HI 3/3 (gnomAD)
Structure: AlphaFold pLDDT 79.27 · 34 PDB
Residue 883: a UniProt-annotated variant site (in men2b; somatic mutation in sporadic medullary thyroid carcinoma; requires 2 nucleotide substitutions); a β-strand; the protein kinase domain

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

Also linked: multiple endocrine neoplasia type 2B multiple endocrine neoplasia type 2

Similar variants

RET p.Ala883Asp Uncertain significance ★★ ⚠ same residue
RET p.Ala883Pro Uncertain significance ★★ ⚠ same residue
RET p.Ala883Thr Uncertain significance ★★ ⚠ same residue
RET p.Ala883= Likely benign ★★ same residue
RET p.Ala883Val Uncertain significance ★ ⚠ same residue
RET p.Ala883Leu Uncertain significance ★ same residue
RET p.Cys634Leu Pathogenic/Likely pathogenic ★★ same condition
RET p.Lys666delinsAsnSer 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-ala883phe (accessed [today's date]).

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