Is MEN1 p.Arg527Ter (c.1579C>T) pathogenic?

MEN1 p.Arg527Ter (c.1579C>T) is classified Pathogenic/Likely pathogenic in MEN1 (ClinVar, Multiple submitters, 14 submitters; last evaluated 2026-04-23). Absent from gnomAD v4.1; Associated with Familial hyperparathyroidism or Hypocalciuric hypercalcaemia.

What condition is associated with MEN1 p.Arg527Ter (c.1579C>T)?

MEN1 p.Arg527Ter (c.1579C>T) is associated with Familial hyperparathyroidism or Hypocalciuric hypercalcaemia, multiple endocrine neoplasia type 1, hereditary neoplastic syndrome (ClinVar).

How common is MEN1 p.Arg527Ter (c.1579C>T) in the general population?

MEN1 p.Arg527Ter (c.1579C>T) is absent from gnomAD v4.1 (gnomAD).

MEN1 p.Arg527Ter

c.1579C>T · rs104894261 · VCV16688

Pathogenic/Likely pathogenic Multiple submitters

Classification

Pathogenic/Likely pathogenic

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 14 submitters

Consequence

nonsense (stop-gain)

predicted LoF

gnomAD v4.1

Absent

absent from gnomAD v4.1

Conditions

Familial hyperparathyroidism or Hypocalciuric hypercalcaemia

Computational evidence

Protein change
Missense predictors do not apply to this variant type; conservation carries the signal.
Consequence	nonsense (stop-gain)	predicted loss-of-function in a haploinsufficient gene (ClinGen)
NMD	escapes	premature termination codon in the last exon (10 of 10) — the truncated protein is likely expressed. PVS1 input, not an applied code
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 6.9	GERP 1.5, phastCons 1
Overall
CADD	46.0	PHRED · no single calibrated threshold — expert panels disagree

Predicted loss-of-function is descriptive, not an applied PVS1 code.

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.Arg527Ter
Coding: c.1579C>T
MANE Select: NM_001370259
dbSNP: rs104894261
Type: single nucleotide variant
Location: chr11:64804588 (GRCh38)
Gene constraint: LOEUF 0.206 · pLI 1.00 · ClinGen HI 3/3 (gnomAD)
Structure: AlphaFold pLDDT 85.13 · 69 PDB
Residue 527: a UniProt-annotated variant site (in men1); the 'disordered' region

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

Disease context

Familial hyperparathyroidism or Hypocalciuric hypercalcaemia

Also linked: multiple endocrine neoplasia type 1 hereditary neoplastic syndrome

Similar variants

MEN1 p.Arg527= Benign/Likely benign ★★ same residue
MEN1 p.Arg527Gln Conflicting classifications of pathogenicity ★ 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
MEN1 c.1351-2A>G 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-arg527ter (accessed [today's date]).

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