Is MEN1 p.Val240= (c.720G>A) pathogenic?

MEN1 p.Val240= (c.720G>A) is classified Benign/Likely benign in MEN1 (ClinVar, Multiple submitters, 2 submitters; last evaluated 2024-11-01). Very rare (popmax 0.0011%, sas); Associated with multiple endocrine neoplasia type 1.

What condition is associated with MEN1 p.Val240= (c.720G>A)?

MEN1 p.Val240= (c.720G>A) is associated with multiple endocrine neoplasia type 1 (ClinVar).

How common is MEN1 p.Val240= (c.720G>A) in the general population?

MEN1 p.Val240= (c.720G>A) is very rare (popmax 0.0011%, sas) (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.Val240=

c.720G>A · rs1555165534 · VCV2875615

Benign/Likely benign Multiple submitters

Classification

Benign/Likely benign

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 2 submitters

gnomAD v4.1

Rare

very rare (popmax 0.0011%, sas)

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 -0.083	GERP 0.32, phastCons 0.54
Overall
CADD	11.59	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.0011% South Asian · 1/91,086 alleles

Overall 6.84e-05% 1/1,461,868 alleles · very rare

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.Val240=
Coding: c.720G>A
MANE Select: NM_001370259
dbSNP: rs1555165534
Type: single nucleotide variant
Location: chr11:64807615 (GRCh38)
Gene constraint: LOEUF 0.206 · pLI 1.00 · ClinGen HI 3/3 (gnomAD)
Structure: AlphaFold pLDDT 85.13 · 69 PDB
Residue 240: the 'interaction with fancd2' region; an α-helix; a UniProt-annotated variant site (in men1)

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

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.Val240Ala Uncertain significance ★★ ⚠ same residue
MEN1 p.Val240Met Uncertain significance ★★ ⚠ same residue
MEN1 p.Val240Leu 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-val240 (accessed [today's date]).

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