Is NF2 p.Ala381Val (c.1142C>T) pathogenic?

NF2 p.Ala381Val (c.1142C>T) is classified Uncertain significance in NF2 (ClinVar, Single submitter, 1 submitter; last evaluated 2023-08-20). AlphaMissense: likely pathogenic (0.8579); Absent from gnomAD v4.1; Associated with familial meningioma.

What condition is associated with NF2 p.Ala381Val (c.1142C>T)?

NF2 p.Ala381Val (c.1142C>T) is associated with familial meningioma (ClinVar).

How common is NF2 p.Ala381Val (c.1142C>T) in the general population?

NF2 p.Ala381Val (c.1142C>T) is absent from gnomAD v4.1 (gnomAD).

How is Meningioma inherited?

Typically Not applicable (Orphanet). A genetic counselor can assess individual risk for a family.

What do computational predictors say about NF2 p.Ala381Val (c.1142C>T)?

AlphaMissense predicts likely pathogenic (score 0.8579) — an in-silico prediction, not a clinical call.

NF2 p.Ala381Val

c.1142C>T · rs2518679215 · VCV2677245

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely pathogenic

0.8579 · ACMG-weighted

gnomAD v4.1

Not reported

no allele count reported in gnomAD v4.1 (AN 1,579,962)

Missense predictors

1/2 damaging

AlphaMissense, SaProt · REVEL no call

Conditions

familial meningioma

Computational evidence

Protein change
AlphaMissense	0.8579	likely pathogenic
REVEL	0.498	indeterminate
SaProt	LLR -9.16	tolerated
⇒ AlphaMissense calls this damaging; SaProt does not; REVEL makes no call.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 7.7	GERP 2.3, phastCons 1
Regional constraint	o/e 0.69	unconstrained · MANE · 69 kb · p 7.9e-12 · regional, not allelic
Overall
CADD	26.6	PHRED · no single calibrated threshold — expert panels disagree

AlphaMissense carries the ACMG weight for missense; REVEL and SaProt are independent agreement signals.

Population frequency

gnomAD v4.1 · exomes + genomes

No allele count reported in gnomAD v4.1 (AN 1,579,962). This is missing data, not an absence: the variant may or may not be present in gnomAD. Rarity (ACMG PM2) and BA1/BS1 cannot be assessed for it.

Variant & gene context

Gene: NF2
Protein: p.Ala381Val
Coding: c.1142C>T
MANE Select: NM_000268
dbSNP: rs2518679215
Type: single nucleotide variant
Location: chr22:29673288 (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

Disease context

familial meningioma — disease report on Sugi Atlas → Associated genes, phenotypes, clinical trials & treatments

For Meningioma (Orphanet):

Inheritance: Not applicable
Onset: All ages
Prevalence: 1-9 / 100 000 (Germany)

Similar variants

NF2 p.Ala381Thr Uncertain significance ★ ⚠ same residue
NF2 p.Arg196Ter Pathogenic ★★ same condition
NF2 c.114+4A>G Uncertain significance ★★ same condition
NF2 p.Ala2Ser Uncertain significance ★★ ⚠ same condition
NF2 p.Arg172Lys Uncertain significance ★★ ⚠ same condition
NF2 p.Arg198Gln Uncertain significance ★★ same condition
NF2 p.Arg225Gln Uncertain significance ★★ ⚠ same condition
NF2 p.Arg25Lys Uncertain significance ★★ ⚠ 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-ala381val (accessed [today's date]).

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