Is NF2 p.Pro479Ser (c.1435C>T) pathogenic?

NF2 p.Pro479Ser (c.1435C>T) is classified Uncertain significance in NF2 (ClinVar, Single submitter, 1 submitter; last evaluated 2025-10-08). AlphaMissense: likely benign (0.0726); Very rare (popmax 0.000952%, nfe); Associated with hereditary neoplastic syndrome.

What condition is associated with NF2 p.Pro479Ser (c.1435C>T)?

NF2 p.Pro479Ser (c.1435C>T) is associated with hereditary neoplastic syndrome (ClinVar).

How common is NF2 p.Pro479Ser (c.1435C>T) in the general population?

NF2 p.Pro479Ser (c.1435C>T) is very rare (popmax 0.000952%, nfe) (gnomAD).

What do computational predictors say about NF2 p.Pro479Ser (c.1435C>T)?

AlphaMissense predicts likely benign (score 0.0726) — an in-silico prediction, not a clinical call.

NF2 p.Pro479Ser

c.1435C>T · VCV4661372

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.0726 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 0.000952%, nfe)

Missense predictors

0/3 damaging

AlphaMissense, REVEL, SaProt

Conditions

hereditary neoplastic syndrome

Computational evidence

Protein change
AlphaMissense	0.0726	likely benign
REVEL	0.207	benign-leaning
SaProt	LLR -9.66	tolerated
⇒ AlphaMissense, REVEL and SaProt all call this tolerated.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 4.2	GERP 2, phastCons 1
Regional constraint	o/e 0.83	unconstrained · MANE · 21 kb · p 0.0072 · regional, not allelic
Overall
CADD	19.12	PHRED · no single calibrated threshold — expert panels disagree

ClinVar classifies this uncertain; the computational predictors unanimously lean tolerated — a triage signal, not a reclassification

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

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.000952% European (non-Finnish) · 11/1,155,010 alleles

Filtering AF 0.000511% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.000374%

Overall 0.000702% 11/1,566,828 alleles · very rare exomes 11/1,414,484 · genomes 0/152,344 · 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.Pro479Ser
Coding: c.1435C>T
MANE Select: NM_000268
Type: single nucleotide variant
Location: chr22:29674930 (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

hereditary neoplastic syndrome — disease report on Sugi Atlas → Associated genes, phenotypes, clinical trials & treatments

Similar variants

NF2 p.Pro479Leu Uncertain significance ★ ⚠ same residue
NF2 p.Pro479Thr Uncertain significance ★ ⚠ same residue
NF2 p.Pro479= Likely benign ★ 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

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-pro479ser (accessed [today's date]).

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