Is MEN1 p.Glu366Asp (c.1098A>T) pathogenic?

MEN1 p.Glu366Asp (c.1098A>T) is classified Conflicting classifications of pathogenicity in MEN1 (ClinVar, Conflicting submitters, 9 submitters; last evaluated 2026-01-17). AlphaMissense: likely benign (0.1558); Ultra-rare (popmax 0.0175%, nfe); Associated with hereditary neoplastic syndrome.

What condition is associated with MEN1 p.Glu366Asp (c.1098A>T)?

MEN1 p.Glu366Asp (c.1098A>T) is associated with hereditary neoplastic syndrome, multiple endocrine neoplasia type 1 (ClinVar).

How common is MEN1 p.Glu366Asp (c.1098A>T) in the general population?

MEN1 p.Glu366Asp (c.1098A>T) is ultra-rare (popmax 0.0175%, nfe) (gnomAD).

What do computational predictors say about MEN1 p.Glu366Asp (c.1098A>T)?

AlphaMissense predicts likely benign (score 0.1558) — an in-silico prediction, not a clinical call.

MEN1 p.Glu366Asp

c.1098A>T · rs149383809 · VCV183065

Conflicting classifications of pathogenicity Conflicting submitters

Classification

Conflicting classifications of pathogenicity

ClinVar

Review

Conflicting submitters ★☆☆☆

ClinVar · 9 submitters

AlphaMissense

likely benign

0.1558 · ACMG-weighted

gnomAD v4.1

Rare

ultra-rare (popmax 0.0175%, nfe)

Conditions

hereditary neoplastic syndrome

Computational evidence

Protein change
AlphaMissense	0.1558	likely benign
REVEL	0.611	indeterminate
Splicing
SpliceAI	<0.2	all four deltas below 0.2 · T>C here scores Δ0.39 · evaluated, not missing
Constraint at this position
Conservation	phyloP -0.4	GERP -0.62, phastCons 0.24
Regional constraint	o/e 0.61	unconstrained · MANE · 4,962 bp · p 4.4e-20 · regional, not allelic
Overall
CADD	14.28	PHRED · no single calibrated threshold — expert panels disagree

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

⚠ Isoform check: AlphaMissense numbered on a different transcript (AM E371D vs ClinVar E366D) — verify the residue.

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.0175% European (non-Finnish) · 207/1,180,014 alleles

Filtering AF 0.0155% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.0148%

Overall 0.0136% 219/1,614,196 alleles · ultra-rare

Ancestry group	Frequency	1 in
European (non-Finnish)grpmax	0.0175%	5,701
Finnishnot grpmax-eligible	0.00937%	10,672
Remaining individualsnot grpmax-eligible	0.0064%	15,627
African / African-American	0.00266%	37,531

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.Glu366Asp
Coding: c.1098A>T
MANE Select: NM_001370259
dbSNP: rs149383809
Type: single nucleotide variant
Location: chr11:64805722 (GRCh38)
Gene constraint: LOEUF 0.206 · pLI 1.00 · ClinGen HI 3/3 (gnomAD)
Structure: AlphaFold pLDDT 85.13 · 69 PDB
Residue 366: the 'interaction with fancd2' region; an α-helix

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.Glu366Ter Pathogenic ★★ same residue
MEN1 p.Glu366= Conflicting classifications of pathogenicity ★ same residue
MEN1 p.Glu366_Val367insTer Pathogenic ★★ 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-glu366asp (accessed [today's date]).

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