Is MEN1 p.Ala182Val (c.545C>T) pathogenic?

MEN1 p.Ala182Val (c.545C>T) is classified Uncertain significance in MEN1 (ClinVar, Single submitter, 1 submitter; last evaluated 2023-11-08). AlphaMissense: likely pathogenic (0.9659); Very rare (popmax 8.47e-05%, nfe); Associated with hereditary neoplastic syndrome.

What condition is associated with MEN1 p.Ala182Val (c.545C>T)?

MEN1 p.Ala182Val (c.545C>T) is associated with hereditary neoplastic syndrome (ClinVar).

How common is MEN1 p.Ala182Val (c.545C>T) in the general population?

MEN1 p.Ala182Val (c.545C>T) is very rare (popmax 8.47e-05%, nfe) (gnomAD).

What do computational predictors say about MEN1 p.Ala182Val (c.545C>T)?

AlphaMissense predicts likely pathogenic (score 0.9659) — an in-silico prediction, not a clinical call.

MEN1 p.Ala182Val

c.545C>T · rs1417432434 · VCV3229104

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely pathogenic

0.9659 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 8.47e-05%, nfe)

Missense predictors

2/2 damaging

AlphaMissense, REVEL

Conditions

hereditary neoplastic syndrome

Computational evidence

Protein change
AlphaMissense	0.9659	likely pathogenic
REVEL	0.888	moderately pathogenic-leaning
⇒ AlphaMissense and REVEL both call this damaging.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 12	GERP 1.4, phastCons 1
Regional constraint	o/e 0.61	unconstrained · MANE · 4,962 bp · p 4.4e-20 · regional, not allelic
Overall
CADD	26.2	PHRED · no single calibrated threshold — expert panels disagree

ClinVar classifies this uncertain; the computational predictors unanimously lean damaging — a triage signal, not a reclassification

AlphaMissense carries the ACMG weight for missense; REVEL and SaProt are independent agreement signals.

⚠ Isoform check: AlphaMissense numbered on a different transcript (AM A187V vs ClinVar A182V) — verify the residue.

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 8.47e-05% European (non-Finnish) · 1/1,180,040 alleles

Overall 6.84e-05% 1/1,461,874 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.Ala182Val
Coding: c.545C>T
MANE Select: NM_001370259
dbSNP: rs1417432434
Type: single nucleotide variant
Location: chr11:64808000 (GRCh38)
Gene constraint: LOEUF 0.206 · pLI 1.00 · ClinGen HI 3/3 (gnomAD)
Structure: AlphaFold pLDDT 85.13 · 69 PDB
Residue 182: a β-strand

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

Similar variants

MEN1 p.Ala182= Likely benign ★★ same residue
MEN1 p.Ala182Pro Uncertain significance ★ ⚠ same residue
MEN1 p.Ala182Thr Uncertain significance ★ ⚠ same residue
MEN1 c.1049+1G>A Pathogenic ★★ same condition
MEN1 c.1049+1G>C Pathogenic ★★ same condition
MEN1 c.1350+1G>A Pathogenic ★★ same condition
MEN1 c.1351-2A>C Pathogenic/Likely pathogenic ★★ same condition
MEN1 c.446-1G>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-ala182val (accessed [today's date]).

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