Is MEN1 p.Thr552= (c.1656T>C) pathogenic?

MEN1 p.Thr552= (c.1656T>C) is classified Benign/Likely benign in MEN1 (ClinVar, Multiple submitters, 7 submitters; last evaluated 2026-01-18). Very rare (popmax 0.00831%, nfe); Associated with hereditary neoplastic syndrome.

What condition is associated with MEN1 p.Thr552= (c.1656T>C)?

MEN1 p.Thr552= (c.1656T>C) is associated with hereditary neoplastic syndrome, multiple endocrine neoplasia type 1 (ClinVar).

How common is MEN1 p.Thr552= (c.1656T>C) in the general population?

MEN1 p.Thr552= (c.1656T>C) is very rare (popmax 0.00831%, nfe) (gnomAD).

MEN1 p.Thr552=

c.1656T>C · rs143423552 · VCV136168

Benign/Likely benign Multiple submitters

Classification

Benign/Likely benign

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 7 submitters

gnomAD v4.1

Rare

very rare (popmax 0.00831%, nfe)

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 0.23	GERP -2.6, phastCons 0.52
Overall
CADD	7.551	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.00831% European (non-Finnish) · 98/1,180,006 alleles

Filtering AF 0.00697% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.00641%

Overall 0.00613% 99/1,614,092 alleles · very rare exomes 96/1,461,826 · genomes 3/152,266 · joint denominator

Ancestry group	Frequency	1 in
European (non-Finnish)grpmax	0.00831%	12,041
Remaining individualsnot grpmax-eligible	0.0016%	62,506

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: MEN1
Protein: p.Thr552=
Coding: c.1656T>C
MANE Select: NM_001370259
dbSNP: rs143423552
Type: single nucleotide variant
Location: chr11:64804511 (GRCh38)
Gene constraint: LOEUF 0.206 · pLI 1.00 · ClinGen HI 3/3 (gnomAD)
Structure: AlphaFold pLDDT 85.13 · 69 PDB
Residue 552: a UniProt-annotated variant site (in adrenal adenoma; somatic); a β-strand; the 'disordered' region

Full MEN1 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 1

Similar variants

MEN1 p.Thr552Ile Uncertain significance ★★ same residue
MEN1 p.Thr552Pro Uncertain significance ★★ ⚠ same residue
MEN1 p.Thr552Ala Uncertain significance ★ same residue
MEN1 p.Thr552Ser Pathogenic ⚠ same residue
MEN1 c.1049+1G>A Pathogenic ★★ same condition
MEN1 c.1049+1G>C Pathogenic ★★ same condition
MEN1 c.1049+2T>C Pathogenic/Likely pathogenic ★★ same condition
MEN1 c.1350+1G>A 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/men1-p-thr552 (accessed [today's date]).

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