Is MN1 p.Pro669Arg (c.2006C>G) pathogenic?

MN1 p.Pro669Arg (c.2006C>G) is classified Uncertain significance in MN1 (ClinVar, Multiple submitters, 2 submitters; last evaluated 2022-03-01). AlphaMissense: likely benign (0.2617); Absent from gnomAD v4.1; Associated with familial meningioma.

What condition is associated with MN1 p.Pro669Arg (c.2006C>G)?

MN1 p.Pro669Arg (c.2006C>G) is associated with familial meningioma, CEBALID syndrome (ClinVar).

How common is MN1 p.Pro669Arg (c.2006C>G) in the general population?

MN1 p.Pro669Arg (c.2006C>G) 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 MN1 p.Pro669Arg (c.2006C>G)?

AlphaMissense predicts likely benign (score 0.2617) — an in-silico prediction, not a clinical call.

MN1 p.Pro669Arg

c.2006C>G · rs1204277623 · VCV1675878

Uncertain significance Multiple submitters

Classification

Uncertain significance

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 2 submitters

AlphaMissense

likely benign

0.2617 · ACMG-weighted

gnomAD v4.1

Not reported

no allele count reported in gnomAD v4.1 (AN 1,520,240)

Missense predictors

0/3 damaging

AlphaMissense, REVEL, SaProt

Conditions

familial meningioma

Computational evidence

Protein change
AlphaMissense	0.2617	likely benign
REVEL	0.126	moderately benign-leaning
SaProt	LLR -8.52	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 7.5	GERP 1.9, phastCons 1
Regional constraint	o/e 0.99	unconstrained · MANE · 50 kb · p 0.63 · regional, not allelic
Overall
CADD	20.9	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

No allele count reported in gnomAD v4.1 (AN 1,520,240). 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: MN1
Protein: p.Pro669Arg
Coding: c.2006C>G
MANE Select: NM_002430
dbSNP: rs1204277623
Type: single nucleotide variant
Location: chr22:27798538 (GRCh38)
Gene constraint: LOEUF 0.482 · pLI 0.99 (gnomAD)
Structure: AlphaFold pLDDT 42.47
Residue 669: a UniProt-annotated variant site (in cebalid); the 'disordered' region

Full MN1 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

Also linked: CEBALID syndrome

For Meningioma (Orphanet):

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

Similar variants

MN1 p.Gln1273Ter Pathogenic ★★ same condition
MN1 p.Lys455Ter Likely pathogenic ★★ same condition
MN1 p.Trp1248Ter Pathogenic/Likely pathogenic ★★ same condition
MN1 p.Gly1092Arg Uncertain significance ★★ ⚠ same condition
MN1 p.Leu706Met Uncertain significance ★★ ⚠ same condition
MN1 p.Pro9Ser Uncertain significance ★★ ⚠ same condition
MN1 p.Ala1318Asp Likely pathogenic ★ ⚠ same condition
MN1 p.Gln1279Ter 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/mn1-p-pro669arg (accessed [today's date]).

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