Is RET p.Arg67= (c.201C>T) pathogenic?

RET p.Arg67= (c.201C>T) is classified Likely benign in RET (ClinVar, Single submitter, 1 submitter; last evaluated 2020-11-03). Very rare (popmax 0.00133%, afr); Associated with multiple endocrine neoplasia type 2.

What condition is associated with RET p.Arg67= (c.201C>T)?

RET p.Arg67= (c.201C>T) is associated with multiple endocrine neoplasia type 2 (ClinVar).

How common is RET p.Arg67= (c.201C>T) in the general population?

RET p.Arg67= (c.201C>T) is very rare (popmax 0.00133%, afr) (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.Arg67=

c.201C>T · rs200328158 · VCV1647573

Likely benign Single submitter

Classification

Likely benign

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

gnomAD v4.1

Rare

very rare (popmax 0.00133%, afr)

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 0.023	GERP 0.54, phastCons 0.002
Overall
CADD	6.23	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.00133% African / African-American · 1/75,060 alleles

Overall 6.2e-05% 1/1,613,930 alleles · very rare exomes 0/1,461,624 · genomes 1/152,306 · 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.Arg67=
Coding: c.201C>T
MANE Select: NM_020975
dbSNP: rs200328158
Type: single nucleotide variant
Location: chr10:43100586 (GRCh38)
Gene constraint: LOEUF 0.24 · pLI 1.00 · ClinGen HI 3/3 (gnomAD)
Structure: AlphaFold pLDDT 79.27 · 34 PDB
Residue 67: a UniProt-annotated variant site (in); 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

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.Arg67Cys Uncertain significance ★★ ⚠ same residue
RET p.Arg67His Benign/Likely benign ★★ same residue
RET p.Arg67Gly Uncertain significance ★ ⚠ same residue
RET p.Arg67Leu Uncertain significance ★ ⚠ same residue
RET c.1879+1G>A Pathogenic/Likely pathogenic ★★ same condition
RET p.Arg180Ter Pathogenic ★★ same condition
RET p.Arg77Cys Pathogenic/Likely pathogenic ★★ ⚠ same condition
RET p.Arg897Ter 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-arg67 (accessed [today's date]).

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