Is MEN1 p.Thr552Ser (c.1654A>T) pathogenic?

MEN1 p.Thr552Ser (c.1654A>T) is classified Pathogenic in MEN1 (ClinVar, No assertion criteria, 1 submitter; last evaluated 1999-12-01). AlphaMissense: likely benign (0.1297); Absent from gnomAD v4.1; Associated with adrenal cortex adenoma.

What condition is associated with MEN1 p.Thr552Ser (c.1654A>T)?

MEN1 p.Thr552Ser (c.1654A>T) is associated with adrenal cortex adenoma (ClinVar).

How common is MEN1 p.Thr552Ser (c.1654A>T) in the general population?

MEN1 p.Thr552Ser (c.1654A>T) is absent from gnomAD v4.1 (gnomAD).

What do computational predictors say about MEN1 p.Thr552Ser (c.1654A>T)?

AlphaMissense predicts likely benign (score 0.1297) — an in-silico prediction, not a clinical call.

MEN1 p.Thr552Ser

c.1654A>T · rs121913035 · VCV16698

Pathogenic No assertion criteria

Classification

Pathogenic

ClinVar

Review

No assertion criteria ☆☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.1297 · ACMG-weighted

gnomAD v4.1

Absent

absent from gnomAD v4.1

Conditions

adrenal cortex adenoma

Computational evidence

Protein change
AlphaMissense	0.1297	likely benign ⚠ discordant with ClinVar
REVEL	0.417	indeterminate
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 6	GERP 1.3, phastCons 1
Regional constraint	o/e 0.33	constrained · MANE · 178 bp · p 1.3e-08 · regional, not allelic
Overall
CADD	20.6	PHRED · no single calibrated threshold — expert panels disagree

AlphaMissense carries the ACMG weight for missense; REVEL and SaProt are independent agreement signals.

⚠ Isoform check: AlphaMissense numbered on a different transcript (AM T557S vs ClinVar T552S) — verify the residue.

Population frequency

gnomAD v4.1 · exomes + genomes

Absent from gnomAD v4.1. Not observed in any sequenced alleles — a rarity signal (ACMG PM2-supporting), not evidence of pathogenicity on its own.

Variant & gene context

Gene: MEN1
Protein: p.Thr552Ser
Coding: c.1654A>T
MANE Select: NM_001370259
dbSNP: rs121913035
Type: single nucleotide variant
Location: chr11:64804513 (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

adrenal cortex adenoma — disease report on Sugi Atlas → Associated genes, phenotypes, clinical trials & treatments

Similar variants

MEN1 p.Thr552Ile Uncertain significance ★★ same residue
MEN1 p.Thr552Pro Uncertain significance ★★ ⚠ same residue
MEN1 p.Thr552= Benign/Likely benign ★★ same residue
MEN1 p.Thr552Ala Uncertain significance ★ same residue
MEN1 c.1049+1G>A Pathogenic ★★ same type
MEN1 c.1049+1G>C Pathogenic ★★ same type
MEN1 c.1049+2T>C Pathogenic/Likely pathogenic ★★ same type
MEN1 c.1350+1G>A Pathogenic ★★ same type

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-thr552ser (accessed [today's date]).

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