Is RET p.Cys620= (c.1860C>T) pathogenic?

RET p.Cys620= (c.1860C>T) is classified Conflicting classifications of pathogenicity in RET (ClinVar, Conflicting submitters, 7 submitters; last evaluated 2025-10-14). Very rare (popmax 0.00334%, amr); Associated with hereditary neoplastic syndrome.

What condition is associated with RET p.Cys620= (c.1860C>T)?

RET p.Cys620= (c.1860C>T) is associated with hereditary neoplastic syndrome, Hirschsprung disease, susceptibility to, 1, familial medullary thyroid carcinoma (ClinVar).

How common is RET p.Cys620= (c.1860C>T) in the general population?

RET p.Cys620= (c.1860C>T) is very rare (popmax 0.00334%, amr) (gnomAD).

RET p.Cys620=

c.1860C>T · rs79890926 · VCV549782

Conflicting classifications of pathogenicity Conflicting submitters

Classification

Conflicting classifications of pathogenicity

ClinVar

Review

Conflicting submitters ★☆☆☆

ClinVar · 7 submitters

gnomAD v4.1

Rare

very rare (popmax 0.00334%, amr)

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 -8.8	GERP -3.4
Overall
CADD	2.532	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.00334% Admixed American · 2/59,962 alleles

Filtering AF 0.000553% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.00026%

Overall 0.000806% 13/1,613,224 alleles · very rare exomes 13/1,460,982 · genomes 0/152,242 · joint denominator

Ancestry group	Frequency	1 in
Admixed Americangrpmax	0.00334%	29,981
African / African-American	0.00267%	37,502
European (non-Finnish)	0.000763%	131,091

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.Cys620=
Coding: c.1860C>T
MANE Select: NM_020975
dbSNP: rs79890926
Type: single nucleotide variant
Location: chr10:43113656 (GRCh38)
Gene constraint: LOEUF 0.24 · pLI 1.00 · ClinGen HI 3/3 (gnomAD)
Structure: AlphaFold pLDDT 79.27 · 34 PDB
Residue 620: a UniProt-annotated variant site (in men2a and mtc; familial form); a UniProt-annotated variant site (in men2a and mtc; familial and sporadic forms); a UniProt-annotated variant site (in men2a, mtc and hscr1; familial and sporadic forms); a UniProt-annotated variant site (in men2a and hscr1); a UniProt-annotated variant site (in men2a); 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: Hirschsprung disease, susceptibility to, 1 familial medullary thyroid carcinoma multiple endocrine neoplasia type 2B pheochromocytoma multiple endocrine neoplasia type 2A multiple endocrine neoplasia type 2

Similar variants

RET p.Cys620Arg Pathogenic ★★ same residue
RET p.Cys620Gly Pathogenic ★★ same residue
RET p.Cys620Phe Pathogenic ★★ same residue
RET p.Cys620Ser Pathogenic ★★ same residue
RET p.Cys620Trp Pathogenic ★★ same residue
RET p.Cys620Tyr Pathogenic ★★ same residue
RET p.Cys620Ter Pathogenic ★ same residue
RET c.1759+1G>A Pathogenic/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-cys620 (accessed [today's date]).

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