Is NF2 p.Arg8= (c.24C>A) pathogenic?

NF2 p.Arg8= (c.24C>A) is classified Likely benign in NF2 (ClinVar, Single submitter, 1 submitter; last evaluated 2025-08-01). Very rare (popmax 0.0035%, amr).

How common is NF2 p.Arg8= (c.24C>A) in the general population?

NF2 p.Arg8= (c.24C>A) is very rare (popmax 0.0035%, amr) (gnomAD).

NF2 p.Arg8=

c.24C>A · VCV4084242

Likely benign Single submitter

Classification

Likely benign

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

gnomAD v4.1

Rare

very rare (popmax 0.0035%, amr)

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 1.9	GERP 1.4, phastCons 1
Overall
CADD	13.58	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.0035% Admixed American · 2/57,100 alleles

Filtering AF 0.000581% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.000217%

Overall 0.000125% 2/1,595,842 alleles · very rare exomes 2/1,443,502 · genomes 0/152,340 · 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.Arg8=
Coding: c.24C>A
MANE Select: NM_000268
Type: single nucleotide variant
Location: chr22:29604022 (GRCh38)
Gene constraint: LOEUF 0.187 · pLI 1.00 · ClinGen HI 3/3 (gnomAD)
Structure: AlphaFold pLDDT 87.85 · 6 PDB

Full NF2 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Similar variants

NF2 p.Arg8His Uncertain significance ★★ ⚠ same residue
NF2 p.Arg8Leu Uncertain significance ★★ ⚠ same residue
NF2 p.Arg8Cys Uncertain significance ★ ⚠ same residue
NF2 p.Arg8Gly Uncertain significance ★ same residue
NF2 p.Arg8Pro Uncertain significance ★ ⚠ same residue
NF2 p.Arg8Ser Conflicting classifications of pathogenicity ★ ⚠ same residue
NF2 p.Arg8Asn Uncertain significance ★★ same residue
NF2 c.115-1G>A 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/nf2-p-arg8 (accessed [today's date]).

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