Is NF2 p.Phe271Cys (c.812T>G) pathogenic?

NF2 p.Phe271Cys (c.812T>G) is classified Uncertain significance in NF2 (ClinVar, Single submitter, 1 submitter; last evaluated 2017-10-31). AlphaMissense: likely pathogenic (0.9928); Absent from gnomAD v4.1.

How common is NF2 p.Phe271Cys (c.812T>G) in the general population?

NF2 p.Phe271Cys (c.812T>G) is absent from gnomAD v4.1 (gnomAD).

What do computational predictors say about NF2 p.Phe271Cys (c.812T>G)?

AlphaMissense predicts likely pathogenic (score 0.9928) — an in-silico prediction, not a clinical call.

NF2 p.Phe271Cys

c.812T>G · rs1555997533 · VCV493339

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely pathogenic

0.9928 · ACMG-weighted

gnomAD v4.1

Absent

absent from gnomAD v4.1

Missense predictors

3/3 damaging

AlphaMissense, REVEL, SaProt

Computational evidence

Protein change
AlphaMissense	0.9928	likely pathogenic
REVEL	0.937	strongly pathogenic-leaning
SaProt	LLR -16.05	damaging
⇒ AlphaMissense, REVEL and SaProt all call this damaging.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 7.9	GERP 2.3, phastCons 1
Regional constraint	o/e 0.69	unconstrained · MANE · 69 kb · p 7.9e-12 · regional, not allelic
Overall
CADD	33.0	PHRED · no single calibrated threshold — expert panels disagree

ClinVar classifies this uncertain; the computational predictors unanimously lean damaging — 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

Absent from gnomAD v4.1. Not observed in any sequenced alleles — a rarity signal (ACMG PM2-supporting), not evidence of pathogenicity on its own.

Variant & gene context

Gene: NF2
Protein: p.Phe271Cys
Coding: c.812T>G
MANE Select: NM_000268
dbSNP: rs1555997533
Type: single nucleotide variant
Location: chr22:29664991 (GRCh38)
Gene constraint: LOEUF 0.187 · pLI 1.00 · ClinGen HI 3/3 (gnomAD)
Structure: AlphaFold pLDDT 87.85 · 6 PDB
Residue 271: the ferm domain; a β-strand

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

Similar variants

NF2 p.Phe271= Likely benign ★★ same residue
NF2 p.Phe271Leu Uncertain significance ★ ⚠ same residue
NF2 p.Phe271Ser Uncertain significance ★ ⚠ same residue
NF2 c.115-1G>A Likely pathogenic ★★ same type
NF2 c.1340+1G>T Pathogenic ★★ same type
NF2 c.1340+2T>G Pathogenic ★★ same type
NF2 c.1447-1G>A Pathogenic ★★ same type
NF2 c.1575-2A>G 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-phe271cys (accessed [today's date]).

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