Is MEN1 p.Ala464= (c.1392G>C) pathogenic?

MEN1 p.Ala464= (c.1392G>C) is classified Benign/Likely benign in MEN1 (ClinVar, Multiple submitters, 3 submitters; last evaluated 2025-08-27). Absent from gnomAD v4.1; Associated with hereditary neoplastic syndrome.

What condition is associated with MEN1 p.Ala464= (c.1392G>C)?

MEN1 p.Ala464= (c.1392G>C) is associated with hereditary neoplastic syndrome, multiple endocrine neoplasia type 1 (ClinVar).

How common is MEN1 p.Ala464= (c.1392G>C) in the general population?

MEN1 p.Ala464= (c.1392G>C) is absent from gnomAD v4.1 (gnomAD).

MEN1 p.Ala464=

c.1392G>C · rs754445482 · VCV1089125

Benign/Likely benign Multiple submitters

Classification

Benign/Likely benign

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 3 submitters

gnomAD v4.1

Absent

absent from gnomAD v4.1

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 -20	GERP -3
Overall
CADD	0.046	PHRED · no single calibrated threshold — expert panels disagree

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.Ala464=
Coding: c.1392G>C
MANE Select: NM_001370259
dbSNP: rs754445482
Type: single nucleotide variant
Location: chr11:64804775 (GRCh38)
Gene constraint: LOEUF 0.206 · pLI 1.00 · ClinGen HI 3/3 (gnomAD)
Structure: AlphaFold pLDDT 85.13 · 69 PDB
Residue 464: the 'disordered' region

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.Ala464Glu Uncertain significance ★★ same residue
MEN1 p.Ala464Pro Uncertain significance ★★ same residue
MEN1 p.Ala464Thr Uncertain significance ★ same residue
MEN1 p.Ala464Val Conflicting classifications of pathogenicity ★ same residue
MEN1 p.Ala464_Glu468del Uncertain significance ★★ same residue
MEN1 p.Ala464_Glu468dup Uncertain significance ★★ same residue
MEN1 p.Ala464fs Pathogenic ★ same residue
MEN1 p.Ala464_Ala465dup Uncertain significance ★ same residue

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-ala464 (accessed [today's date]).

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