Is MEN1 p.Leu10= (c.30G>T) pathogenic?

MEN1 p.Leu10= (c.30G>T) is classified Conflicting classifications of pathogenicity in MEN1 (ClinVar, Conflicting submitters, 15 submitters; last evaluated 2026-02-04). Ultra-rare (popmax 0.0375%, nfe); Associated with hyperparathyroidism.

What condition is associated with MEN1 p.Leu10= (c.30G>T)?

MEN1 p.Leu10= (c.30G>T) is associated with hyperparathyroidism, multiple endocrine neoplasia type 1, hereditary neoplastic syndrome (ClinVar).

How common is MEN1 p.Leu10= (c.30G>T) in the general population?

MEN1 p.Leu10= (c.30G>T) is ultra-rare (popmax 0.0375%, nfe) (gnomAD).

MEN1 p.Leu10=

c.30G>T · rs371192390 · VCV136169

Conflicting classifications of pathogenicity Conflicting submitters

Classification

Conflicting classifications of pathogenicity

ClinVar

Review

Conflicting submitters ★☆☆☆

ClinVar · 15 submitters

gnomAD v4.1

Rare

ultra-rare (popmax 0.0375%, nfe)

Conditions

hyperparathyroidism

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 0.12	GERP -1.6, phastCons 0.93
Overall
CADD	12.02	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.0375% European (non-Finnish) · 441/1,177,374 alleles

Filtering AF 0.0345% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.0334%

Overall 0.0557% 894/1,604,882 alleles · ultra-rare

Ancestry group	Frequency	1 in
Finnishnot grpmax-eligible	0.595%	168
Ashkenazi Jewishnot grpmax-eligible	0.132%	755
Remaining individualsnot grpmax-eligible	0.0515%	1,942
European (non-Finnish)grpmax	0.0375%	2,670
Middle Eastern	0.0334%	2,998
South Asian	0.02%	5,001
Admixed American	0.00505%	19,815
African / African-American	0.00134%	74,788

Finnish shows a higher raw frequency than the grpmax group above it. gnomAD excludes bottlenecked groups — Finnish, Ashkenazi Jewish, Amish and “Remaining individuals” — from grpmax, because founder effects make their frequencies unrepresentative for filtering. The table is sorted by frequency, so an excluded group can sit above the grpmax row.

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.Leu10=
Coding: c.30G>T
MANE Select: NM_001370259
dbSNP: rs371192390
Type: single nucleotide variant
Location: chr11:64810080 (GRCh38)
Gene constraint: LOEUF 0.206 · pLI 1.00 · ClinGen HI 3/3 (gnomAD)
Structure: AlphaFold pLDDT 85.13 · 69 PDB

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

Disease context

hyperparathyroidism — disease report on Sugi Atlas → Associated genes, phenotypes, clinical trials & treatments

Also linked: multiple endocrine neoplasia type 1 hereditary neoplastic syndrome

Similar variants

MEN1 p.Leu10Arg Uncertain significance ★★ ⚠ same residue
MEN1 p.Leu10Gln Uncertain significance ★ ⚠ same residue
MEN1 p.Leu10Pro Uncertain significance ★ ⚠ same residue
MEN1 p.Leu10Val 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

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-leu10 (accessed [today's date]).

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