Is MEN1 p.Pro79Arg (c.236C>G) pathogenic?

MEN1 p.Pro79Arg (c.236C>G) is classified Conflicting classifications of pathogenicity in MEN1 (ClinVar, Conflicting submitters, 4 submitters; last evaluated 2026-01-26). AlphaMissense: likely pathogenic (0.9942); Very rare (popmax 0.00332%, sas); Associated with multiple endocrine neoplasia type 1.

What condition is associated with MEN1 p.Pro79Arg (c.236C>G)?

MEN1 p.Pro79Arg (c.236C>G) is associated with multiple endocrine neoplasia type 1, hereditary neoplastic syndrome (ClinVar).

How common is MEN1 p.Pro79Arg (c.236C>G) in the general population?

MEN1 p.Pro79Arg (c.236C>G) is very rare (popmax 0.00332%, 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.

What do computational predictors say about MEN1 p.Pro79Arg (c.236C>G)?

AlphaMissense predicts likely pathogenic (score 0.9942) — an in-silico prediction, not a clinical call.

MEN1 p.Pro79Arg

c.236C>G · rs1555166557 · VCV527276

Conflicting classifications of pathogenicity Conflicting submitters

Classification

Conflicting classifications of pathogenicity

ClinVar

Review

Conflicting submitters ★☆☆☆

ClinVar · 4 submitters

AlphaMissense

likely pathogenic

0.9942 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 0.00332%, sas)

Missense predictors

2/3 damaging

AlphaMissense, REVEL, SaProt

Conditions

multiple endocrine neoplasia type 1

Computational evidence

Protein change
AlphaMissense	0.9942	likely pathogenic
REVEL	0.942	strongly pathogenic-leaning
SaProt	LLR -7.24	tolerated
⇒ AlphaMissense and REVEL call this damaging; SaProt does not.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 12	GERP 1.6, phastCons 1
Regional constraint	o/e 0.61	unconstrained · MANE · 4,962 bp · p 4.4e-20 · regional, not allelic
Overall
CADD	33.0	PHRED · no single calibrated threshold — expert panels disagree

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

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.00332% South Asian · 3/90,422 alleles

Filtering AF 0.000881% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.000444%

Overall 0.000187% 3/1,606,076 alleles · very rare exomes 3/1,453,918 · genomes 0/152,158 · 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.Pro79Arg
Coding: c.236C>G
MANE Select: NM_001370259
dbSNP: rs1555166557
Type: single nucleotide variant
Location: chr11:64809874 (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

multiple endocrine neoplasia type 1 — disease report on Sugi Atlas → Associated genes, phenotypes, clinical trials & treatments

Also linked: hereditary neoplastic syndrome

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.Pro79Leu Uncertain significance ★★ ⚠ same residue
MEN1 p.Pro79Ser Uncertain significance ★★ ⚠ same residue
MEN1 p.Pro79= Likely benign ★★ same residue
MEN1 p.Pro79Ala Uncertain significance ★ ⚠ same residue
MEN1 p.Pro79Thr Uncertain significance ★ ⚠ same residue
MEN1 p.Pro79fs Pathogenic ★★ same residue
MEN1 c.1049+1G>A Pathogenic ★★ same condition
MEN1 c.1049+1G>C 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-pro79arg (accessed [today's date]).

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