Is MEN1 p.Asp82= (c.246C>T) pathogenic?

MEN1 p.Asp82= (c.246C>T) is classified Likely benign in MEN1 (ClinVar, Multiple submitters, 2 submitters; last evaluated 2024-04-09). Very rare (popmax 8.49e-05%, nfe); Associated with hereditary neoplastic syndrome.

What condition is associated with MEN1 p.Asp82= (c.246C>T)?

MEN1 p.Asp82= (c.246C>T) is associated with hereditary neoplastic syndrome, multiple endocrine neoplasia type 1 (ClinVar).

How common is MEN1 p.Asp82= (c.246C>T) in the general population?

MEN1 p.Asp82= (c.246C>T) is very rare (popmax 8.49e-05%, nfe) (gnomAD).

MEN1 p.Asp82=

c.246C>T · rs1238113583 · VCV1546459

Likely benign Multiple submitters

Classification

Likely benign

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 2 submitters

gnomAD v4.1

Rare

very rare (popmax 8.49e-05%, 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 5.2	GERP -0.61, phastCons 1
Overall
CADD	12.83	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 8.49e-05% European (non-Finnish) · 1/1,177,548 alleles

Overall 6.22e-05% 1/1,608,792 alleles · very rare exomes 1/1,456,744 · genomes 0/152,048 · joint denominator

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.Asp82=
Coding: c.246C>T
MANE Select: NM_001370259
dbSNP: rs1238113583
Type: single nucleotide variant
Location: chr11:64809864 (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

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.Asp82His Uncertain significance ★★ ⚠ same residue
MEN1 p.Asp82Tyr Uncertain significance ★★ ⚠ same residue
MEN1 p.Asp82Glu Benign/Likely benign ★★ same residue
MEN1 p.Asp82Ala Uncertain significance ★ ⚠ same residue
MEN1 p.Asp82Asn 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

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-asp82 (accessed [today's date]).

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