Is MEN1 p.Cys230Arg (c.688T>C) pathogenic?

MEN1 p.Cys230Arg (c.688T>C) is classified Likely pathogenic in MEN1 (ClinVar, Single submitter, 1 submitter; last evaluated 2023-01-31). AlphaMissense: likely pathogenic (0.9993); Absent from gnomAD v4.1.

How common is MEN1 p.Cys230Arg (c.688T>C) in the general population?

MEN1 p.Cys230Arg (c.688T>C) is absent from gnomAD v4.1 (gnomAD).

What do computational predictors say about MEN1 p.Cys230Arg (c.688T>C)?

AlphaMissense predicts likely pathogenic (score 0.9993) — an in-silico prediction, not a clinical call.

MEN1 p.Cys230Arg

c.688T>C · rs1555165570 · VCV449057

Likely pathogenic Single submitter

Classification

Likely pathogenic

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely pathogenic

0.9993 · ACMG-weighted

gnomAD v4.1

Absent

absent from gnomAD v4.1

Missense predictors

2/2 damaging

AlphaMissense, REVEL

Computational evidence

Protein change
AlphaMissense	0.9993	likely pathogenic ✓ concordant with ClinVar · top 4% in MEN1
REVEL	0.959	strongly 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 11	GERP 1.5, phastCons 1
Regional constraint	o/e 0.61	unconstrained · MANE · 4,962 bp · p 4.4e-20 · regional, not allelic
Overall
CADD	28.5	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 C235R vs ClinVar C230R) — verify the residue.

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.Cys230Arg
Coding: c.688T>C
MANE Select: NM_001370259
dbSNP: rs1555165570
Type: single nucleotide variant
Location: chr11:64807647 (GRCh38)
Gene constraint: LOEUF 0.206 · pLI 1.00 · ClinGen HI 3/3 (gnomAD)
Structure: AlphaFold pLDDT 85.13 · 69 PDB
Residue 230: the 'interaction with fancd2' region

Full MEN1 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Similar variants

MEN1 p.Cys230Tyr Uncertain significance ★★ ⚠ same residue
MEN1 p.Cys230= Likely benign ★★ same residue
MEN1 p.Cys230Ter Pathogenic ★ same residue
MEN1 p.Cys230Phe Uncertain significance ★ ⚠ same residue
MEN1 p.Cys230fs Pathogenic ★★ same residue
MEN1 c.1049+1G>A Pathogenic ★★ same type
MEN1 c.1049+1G>C Pathogenic ★★ same type
MEN1 c.1049+2T>C Pathogenic/Likely pathogenic ★★ same type

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-cys230arg (accessed [today's date]).

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