Is MEN1 p.Pro595= (c.1785T>A) pathogenic?

MEN1 p.Pro595= (c.1785T>A) is classified Likely benign in MEN1 (ClinVar, Single submitter, 1 submitter; last evaluated 2023-12-13). Absent from gnomAD v4.1; Associated with hereditary neoplastic syndrome.

What condition is associated with MEN1 p.Pro595= (c.1785T>A)?

MEN1 p.Pro595= (c.1785T>A) is associated with hereditary neoplastic syndrome (ClinVar).

How common is MEN1 p.Pro595= (c.1785T>A) in the general population?

MEN1 p.Pro595= (c.1785T>A) is absent from gnomAD v4.1 (gnomAD).

MEN1 p.Pro595=

c.1785T>A · rs2497100114 · VCV3229084

Likely benign Single submitter

Classification

Likely benign

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

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 3.1	GERP 0.43, phastCons 1
Overall
CADD	11.63	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.Pro595=
Coding: c.1785T>A
MANE Select: NM_001370259
dbSNP: rs2497100114
Type: single nucleotide variant
Location: chr11:64804382 (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

hereditary neoplastic syndrome — disease report on Sugi Atlas → Associated genes, phenotypes, clinical trials & treatments

Similar variants

MEN1 p.Pro595Thr Uncertain significance ★ same residue
MEN1 p.Pro595Arg Uncertain significance ★ same residue
MEN1 p.Pro595Ser 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-pro595 (accessed [today's date]).

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