Is MEN1 p.Pro69Ser (c.205C>T) pathogenic?

MEN1 p.Pro69Ser (c.205C>T) is classified Conflicting classifications of pathogenicity in MEN1 (ClinVar, Conflicting submitters, 4 submitters; last evaluated 2025-06-23). AlphaMissense: likely benign (0.0875); Absent from gnomAD v4.1; Associated with MEN1-related disorder.

What condition is associated with MEN1 p.Pro69Ser (c.205C>T)?

MEN1 p.Pro69Ser (c.205C>T) is associated with MEN1-related disorder, multiple endocrine neoplasia type 1, hereditary neoplastic syndrome (ClinVar).

How common is MEN1 p.Pro69Ser (c.205C>T) in the general population?

MEN1 p.Pro69Ser (c.205C>T) is absent from gnomAD v4.1 (gnomAD).

What do computational predictors say about MEN1 p.Pro69Ser (c.205C>T)?

AlphaMissense predicts likely benign (score 0.0875) — an in-silico prediction, not a clinical call.

MEN1 p.Pro69Ser

c.205C>T · rs1060499995 · VCV403846

Conflicting classifications of pathogenicity Conflicting submitters

Classification

Conflicting classifications of pathogenicity

ClinVar

Review

Conflicting submitters ★☆☆☆

ClinVar · 4 submitters

AlphaMissense

likely benign

0.0875 · ACMG-weighted

gnomAD v4.1

Absent

absent from gnomAD v4.1

Missense predictors

0/2 damaging

AlphaMissense, SaProt · REVEL no call

Conditions

MEN1-related disorder

Computational evidence

Protein change
AlphaMissense	0.0875	likely benign
REVEL	0.585	indeterminate
SaProt	LLR -8.62	tolerated
⇒ AlphaMissense and SaProt both call this tolerated; REVEL makes no call.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 9.8	GERP 0.58, phastCons 1
Regional constraint	o/e 0.61	unconstrained · MANE · 4,962 bp · p 4.4e-20 · regional, not allelic
Overall
CADD	22.1	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

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.Pro69Ser
Coding: c.205C>T
MANE Select: NM_001370259
dbSNP: rs1060499995
Type: single nucleotide variant
Location: chr11:64809905 (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

MEN1-related disorder

Also linked: multiple endocrine neoplasia type 1 hereditary neoplastic syndrome

Similar variants

MEN1 p.Pro69Ala Uncertain significance ★ ⚠ same residue
MEN1 p.Pro69Leu Uncertain significance ★ ⚠ same residue
MEN1 p.Pro69= Likely benign ★ 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-pro69ser (accessed [today's date]).

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