Is RET p.Arg231= (c.693C>T) pathogenic?

RET p.Arg231= (c.693C>T) is classified Benign/Likely benign in RET (ClinVar, Multiple submitters, 7 submitters; last evaluated 2026-01-21). Rare (popmax 0.153%, eas); Associated with hereditary neoplastic syndrome.

What condition is associated with RET p.Arg231= (c.693C>T)?

RET p.Arg231= (c.693C>T) is associated with hereditary neoplastic syndrome, multiple endocrine neoplasia type 2B, multiple endocrine neoplasia type 2A (ClinVar).

How common is RET p.Arg231= (c.693C>T) in the general population?

RET p.Arg231= (c.693C>T) is rare (popmax 0.153%, eas) (gnomAD).

RET p.Arg231=

c.693C>T · rs576806329 · VCV136123

Benign/Likely benign Multiple submitters

Classification

Benign/Likely benign

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 7 submitters

gnomAD v4.1

Rare

rare (popmax 0.153%, eas)

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 · no allele here is in the release
Constraint at this position
Conservation	phyloP -9.2	GERP -4.2
Overall
CADD	6.537	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.153% East Asian · 68/44,588 alleles

Filtering AF 0.123% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.113%

Overall 0.00456% 73/1,599,928 alleles · rare exomes 64/1,447,658 · genomes 9/152,270 · joint denominator

Ancestry group	Frequency	1 in
East Asiangrpmax	0.153%	656
Remaining individualsnot grpmax-eligible	0.00805%	12,421

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.Arg231=
Coding: c.693C>T
MANE Select: NM_020975
dbSNP: rs576806329
Type: single nucleotide variant
Location: chr10:43105019 (GRCh38)
Gene constraint: LOEUF 0.24 · pLI 1.00 · ClinGen HI 3/3 (gnomAD)
Structure: AlphaFold pLDDT 79.27 · 34 PDB
Residue 231: a UniProt-annotated variant site (in hscr1; familial form); a turn; the cadherin 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 2A multiple endocrine neoplasia type 2

Similar variants

RET p.Arg231Cys 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
RET p.Arg77Cys Pathogenic/Likely pathogenic ★★ ⚠ same condition
RET p.Arg873Trp Likely pathogenic ★★ same condition
RET p.Arg897Ter Pathogenic ★★ same condition
RET p.Asp631Tyr 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-arg231 (accessed [today's date]).

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