Is NF2 p.Asp85= (c.255T>C) pathogenic?

NF2 p.Asp85= (c.255T>C) is classified Conflicting classifications of pathogenicity in NF2 (ClinVar, Conflicting submitters, 8 submitters; last evaluated 2025-12-15). Ultra-rare (popmax 0.0183%, amr); Associated with hereditary neoplastic syndrome.

What condition is associated with NF2 p.Asp85= (c.255T>C)?

NF2 p.Asp85= (c.255T>C) is associated with hereditary neoplastic syndrome, NF2-related schwannomatosis (ClinVar).

How common is NF2 p.Asp85= (c.255T>C) in the general population?

NF2 p.Asp85= (c.255T>C) is ultra-rare (popmax 0.0183%, amr) (gnomAD).

NF2 p.Asp85=

c.255T>C · rs375802248 · VCV457910

Conflicting classifications of pathogenicity Conflicting submitters

Classification

Conflicting classifications of pathogenicity

ClinVar

Review

Conflicting submitters ★☆☆☆

ClinVar · 8 submitters

gnomAD v4.1

Rare

ultra-rare (popmax 0.0183%, amr)

Conditions

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 -1.9	GERP -4.3
Overall
CADD	4.298	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.0183% Admixed American · 11/60,006 alleles

Filtering AF 0.0102% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.00785%

Overall 0.00173% 28/1,614,114 alleles · ultra-rare exomes 23/1,461,886 · genomes 5/152,228 · joint denominator

Ancestry group	Frequency	1 in
Admixed Americangrpmax	0.0183%	5,455
Middle Eastern	0.0164%	6,084
Remaining individualsnot grpmax-eligible	0.0096%	10,415
East Asian	0.00223%	44,904
African / African-American	0.00133%	74,928
South Asian	0.0011%	91,096
European (non-Finnish)	0.000593%	168,578

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.Asp85=
Coding: c.255T>C
MANE Select: NM_000268
dbSNP: rs375802248
Type: single nucleotide variant
Location: chr22:29639104 (GRCh38)
Gene constraint: LOEUF 0.187 · pLI 1.00 · ClinGen HI 3/3 (gnomAD)
Structure: AlphaFold pLDDT 87.85 · 6 PDB
Residue 85: the ferm domain; a β-strand

Full NF2 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: NF2-related schwannomatosis

Similar variants

NF2 p.Asp85Gly Uncertain significance ★ same residue
NF2 p.Asp85His Uncertain significance ★ ⚠ same residue
NF2 p.Asp85del Uncertain significance ★ same residue
NF2 c.115-1G>A Likely pathogenic ★★ same condition
NF2 c.1340+1G>T Pathogenic ★★ same condition
NF2 c.1340+2T>G Pathogenic ★★ same condition
NF2 c.1447-1G>A Pathogenic ★★ same condition
NF2 c.1575-2A>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/nf2-p-asp85 (accessed [today's date]).

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