Is NF2 p.Val24Ala (c.71T>C) pathogenic?

NF2 p.Val24Ala (c.71T>C) is classified Conflicting classifications of pathogenicity in NF2 (ClinVar, Conflicting submitters, 4 submitters; last evaluated 2025-11-10). AlphaMissense: likely pathogenic (0.7975); Very rare (popmax 0.00507%, amr); Associated with hereditary neoplastic syndrome.

What condition is associated with NF2 p.Val24Ala (c.71T>C)?

NF2 p.Val24Ala (c.71T>C) is associated with hereditary neoplastic syndrome, NF2-related schwannomatosis (ClinVar).

How common is NF2 p.Val24Ala (c.71T>C) in the general population?

NF2 p.Val24Ala (c.71T>C) is very rare (popmax 0.00507%, amr) (gnomAD).

What do computational predictors say about NF2 p.Val24Ala (c.71T>C)?

AlphaMissense predicts likely pathogenic (score 0.7975) — an in-silico prediction, not a clinical call.

NF2 p.Val24Ala

c.71T>C · rs773714780 · VCV826903

Conflicting classifications of pathogenicity Conflicting submitters

Classification

Conflicting classifications of pathogenicity

ClinVar

Review

Conflicting submitters ★☆☆☆

ClinVar · 4 submitters

AlphaMissense

likely pathogenic

0.7975 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 0.00507%, amr)

Missense predictors

1/2 damaging

AlphaMissense, SaProt · REVEL indeterminate

Conditions

hereditary neoplastic syndrome

Computational evidence

Protein change
AlphaMissense	0.7975	likely pathogenic
REVEL	0.617	indeterminate
SaProt	LLR -4.08	tolerated
⇒ AlphaMissense calls this damaging; SaProt does not; REVEL is indeterminate.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 6	GERP 0.42, phastCons 1
Regional constraint	o/e 0.69	unconstrained · MANE · 69 kb · p 7.9e-12 · regional, not allelic
Overall
CADD	29.6	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

Grpmax group 0.00507% Admixed American · 3/59,204 alleles

Filtering AF 0.00135% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.000673%

Overall 0.000187% 3/1,607,966 alleles · very rare exomes 3/1,455,672 · genomes 0/152,294 · 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.Val24Ala
Coding: c.71T>C
MANE Select: NM_000268
dbSNP: rs773714780
Type: single nucleotide variant
Location: chr22:29604069 (GRCh38)
Gene constraint: LOEUF 0.187 · pLI 1.00 · ClinGen HI 3/3 (gnomAD)
Structure: AlphaFold pLDDT 87.85 · 6 PDB
Residue 24: 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.Val24Met Uncertain significance ★★ ⚠ same residue
NF2 p.Val24= Likely benign ★★ same residue
NF2 p.Val24Gly Uncertain significance ★ ⚠ same residue
NF2 p.Val24Leu Uncertain significance ★ ⚠ same residue
NF2 p.Val24fs Pathogenic ★ 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

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-val24ala (accessed [today's date]).

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