Is MEN1 p.Pro72= (c.216T>G) pathogenic?

MEN1 p.Pro72= (c.216T>G) is classified Likely benign in MEN1 (ClinVar, Multiple submitters, 3 submitters; last evaluated 2024-12-10). Very rare (popmax 0.00233%, eas); Associated with multiple endocrine neoplasia type 1.

What condition is associated with MEN1 p.Pro72= (c.216T>G)?

MEN1 p.Pro72= (c.216T>G) is associated with multiple endocrine neoplasia type 1, hereditary neoplastic syndrome (ClinVar).

How common is MEN1 p.Pro72= (c.216T>G) in the general population?

MEN1 p.Pro72= (c.216T>G) is very rare (popmax 0.00233%, eas) (gnomAD).

How is Multiple endocrine neoplasia type 1 inherited?

Typically Autosomal dominant, Not applicable (Orphanet). A genetic counselor can assess individual risk for a family.

MEN1 p.Pro72=

c.216T>G · rs1592659467 · VCV1090390

Likely benign Multiple submitters

Classification

Likely benign

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 3 submitters

gnomAD v4.1

Rare

very rare (popmax 0.00233%, eas)

Conditions

multiple endocrine neoplasia type 1

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 -4.8	GERP -3.3
Overall
CADD	4.693	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.00233% East Asian · 1/42,962 alleles

Filtering AF 0.0011% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.000885%

Overall 0.00153% 21/1,374,058 alleles · very rare

Ancestry group	Frequency	1 in
East Asiangrpmax	0.00233%	42,962
European (non-Finnish)	0.00172%	58,216
African / African-American	0.00141%	70,810

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.Pro72=
Coding: c.216T>G
MANE Select: NM_001370259
dbSNP: rs1592659467
Type: single nucleotide variant
Location: chr11:64809894 (GRCh38)
Gene constraint: LOEUF 0.206 · pLI 1.00 · ClinGen HI 3/3 (gnomAD)
Structure: AlphaFold pLDDT 85.13 · 69 PDB
Residue 72: a turn

Full MEN1 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Disease context

multiple endocrine neoplasia type 1 — disease report on Sugi Atlas → Associated genes, phenotypes, clinical trials & treatments

Also linked: hereditary neoplastic syndrome

For Multiple endocrine neoplasia type 1 (Orphanet):

Inheritance: Autosomal dominant, Not applicable
Onset: All ages
Prevalence: 1-9 / 100 000 (Europe)

Similar variants

MEN1 p.Pro72His Uncertain significance ★★ ⚠ same residue
MEN1 p.Pro72Leu Uncertain significance ★ ⚠ same residue
MEN1 p.Pro72Ser Uncertain significance ★ ⚠ 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
MEN1 c.1351-2A>C 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/men1-p-pro72 (accessed [today's date]).

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