NF2 p.Lys124=
c.372G>A · VCV4825432
Likely benign
Single submitter
Classification
Likely benign
ClinVar
Review
Single submitter ★☆☆☆
ClinVar · 1 submitter
gnomAD v4.1
Rare
very rare (popmax 8.48e-05%, nfe)
Conditions
1
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 3.8 | GERP -1.1, phastCons 1 |
| Overall | ||
| CADD | 10.28 | PHRED · no single calibrated threshold — expert panels disagree |
Population frequency
gnomAD v4.1 · exomes + genomes
Grpmax group
8.48e-05%
European (non-Finnish) · 1/1,179,796 alleles
Overall
6.2e-05%
1/1,613,892 alleles · very rare
exomes 1/1,461,588 · genomes 0/152,304 · joint denominator
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
- NF2
- Protein
- p.Lys124=
- Coding
- c.372G>A
- MANE Select
- NM_000268
- Type
- single nucleotide variant
- Location
- chr22:29642210 (GRCh38)
- Gene constraint
- LOEUF 0.187 · pLI 1.00 · ClinGen HI 3/3 (gnomAD)
- Structure
- AlphaFold pLDDT 87.85 · 6 PDB
- Residue 124
- the ferm domain; a UniProt-annotated variant site (in sporadic meningioma); an α-helix
Similar variants
- NF2 p.Lys124Gln Uncertain significance ★★ ⚠ same residue
- NF2 p.Lys124Asn Uncertain significance ★ same residue
- NF2 c.1575-2A>G Pathogenic ★★ same condition
- NF2 c.1737+1G>T Pathogenic ★★ same condition
- NF2 c.1737+2T>C Pathogenic/Likely pathogenic ★★ same condition
- NF2 c.240+1G>A Pathogenic/Likely pathogenic ★★ same condition
- NF2 c.240+1G>C Pathogenic ★★ same condition
- NF2 c.240+1G>T 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/nf2-p-lys124 (accessed [today's date]).
Preprint & method: sugi.bio/variant/method Machine-readable: this page as Markdown