Is RET p.Asp631= (c.1893C>T) pathogenic?

RET p.Asp631= (c.1893C>T) is classified Benign/Likely benign in RET (ClinVar, Multiple submitters, 9 submitters; last evaluated 2026-02-02). Ultra-rare (popmax 0.0187%, afr); Associated with hereditary neoplastic syndrome.

What condition is associated with RET p.Asp631= (c.1893C>T)?

RET p.Asp631= (c.1893C>T) is associated with hereditary neoplastic syndrome, multiple endocrine neoplasia type 2A, multiple endocrine neoplasia type 2 (ClinVar).

How common is RET p.Asp631= (c.1893C>T) in the general population?

RET p.Asp631= (c.1893C>T) is ultra-rare (popmax 0.0187%, afr) (gnomAD).

RET p.Asp631=

c.1893C>T · rs55846256 · VCV24919

Benign/Likely benign Multiple submitters

Classification

Benign/Likely benign

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 9 submitters

gnomAD v4.1

Rare

ultra-rare (popmax 0.0187%, afr)

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 -11	GERP -3.7
Overall
CADD	0.253	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.0187% African / African-American · 14/74,994 alleles

Filtering AF 0.0122% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.0116%

Overall 0.0121% 194/1,607,216 alleles · ultra-rare

Ancestry group	Frequency	1 in
African / African-Americangrpmax	0.0187%	5,357
European (non-Finnish)	0.014%	7,151
Admixed American	0.0117%	8,573
Finnishnot grpmax-eligible	0.00698%	14,323
Remaining individualsnot grpmax-eligible	0.0064%	15,615

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.Asp631=
Coding: c.1893C>T
MANE Select: NM_020975
dbSNP: rs55846256
Type: single nucleotide variant
Location: chr10:43114493 (GRCh38)
Gene constraint: LOEUF 0.24 · pLI 1.00 · ClinGen HI 3/3 (gnomAD)
Structure: AlphaFold pLDDT 79.27 · 34 PDB
Residue 631: a UniProt-annotated variant site (in thyroid carcinoma; somatic mutation); a disulfide bond

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 2A multiple endocrine neoplasia type 2

Similar variants

RET p.Asp631Tyr Pathogenic ★★ ⚠ same residue
RET p.Asp631Glu Uncertain significance ★★ ⚠ same residue
RET p.Asp631Asn Conflicting classifications of pathogenicity ★ ⚠ same residue
RET p.Asp631Val Conflicting classifications of pathogenicity ★ ⚠ same residue
RET p.Asp631del 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-asp631 (accessed [today's date]).

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