Is MEN1 p.His199= (c.597C>T) pathogenic?

MEN1 p.His199= (c.597C>T) is classified Benign/Likely benign in MEN1 (ClinVar, Multiple submitters, 14 submitters; last evaluated 2026-02-04). Rare (popmax 0.646%, afr); Associated with hereditary neoplastic syndrome.

What condition is associated with MEN1 p.His199= (c.597C>T)?

MEN1 p.His199= (c.597C>T) is associated with hereditary neoplastic syndrome, multiple endocrine neoplasia type 1 (ClinVar).

How common is MEN1 p.His199= (c.597C>T) in the general population?

MEN1 p.His199= (c.597C>T) is rare (popmax 0.646%, afr) (gnomAD).

MEN1 p.His199=

c.597C>T · rs150512958 · VCV132740

Benign/Likely benign Multiple submitters

Classification

Benign/Likely benign

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 14 submitters

gnomAD v4.1

Rare

rare (popmax 0.646%, afr)

Conditions

hereditary neoplastic syndrome

Computational evidence

Protein change
Missense predictors do not apply to this variant type; conservation carries the signal.
Splicing
SpliceAI	<0.2	all four deltas below 0.2 · G>T here scores Δ0.27 · evaluated, not missing
Constraint at this position
Conservation	phyloP -1	GERP -2.9
Overall
CADD	5.671	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.646% African / African-American · 485/75,044 alleles

Filtering AF 0.599% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.58%

Overall 0.0338% 545/1,614,190 alleles · rare

Ancestry group	Frequency	1 in
African / African-Americangrpmax	0.646%	155
Remaining individualsnot grpmax-eligible	0.0528%	1,894
Admixed American	0.0317%	3,159
Middle Eastern	0.0165%	6,062
South Asian	0.0011%	91,082
European (non-Finnish)	0.000508%	196,671

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.His199=
Coding: c.597C>T
MANE Select: NM_001370259
dbSNP: rs150512958
Type: single nucleotide variant
Location: chr11:64807948 (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

Also linked: multiple endocrine neoplasia type 1

Similar variants

MEN1 p.His199Tyr Uncertain significance ★ ⚠ same residue
MEN1 p.His199Gln Uncertain significance ★ ⚠ 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-his199 (accessed [today's date]).

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