Is NF1 p.Arg2183Pro (c.6548G>C) pathogenic?

NF1 p.Arg2183Pro (c.6548G>C) is classified Uncertain significance in NF1 (ClinVar, Multiple submitters, 2 submitters; last evaluated 2024-07-11). AlphaMissense: likely pathogenic (0.8672); Absent from gnomAD v4.1; Associated with hereditary neoplastic syndrome.

What condition is associated with NF1 p.Arg2183Pro (c.6548G>C)?

NF1 p.Arg2183Pro (c.6548G>C) is associated with hereditary neoplastic syndrome, neurofibromatosis type 1 (ClinVar).

How common is NF1 p.Arg2183Pro (c.6548G>C) in the general population?

NF1 p.Arg2183Pro (c.6548G>C) is absent from gnomAD v4.1 (gnomAD).

What do computational predictors say about NF1 p.Arg2183Pro (c.6548G>C)?

AlphaMissense predicts likely pathogenic (score 0.8672) — an in-silico prediction, not a clinical call.

NF1 p.Arg2183Pro

c.6548G>C · rs2069706142 · VCV963300

Uncertain significance Multiple submitters

Classification

Uncertain significance

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 2 submitters

AlphaMissense

likely pathogenic

0.8672 · ACMG-weighted

gnomAD v4.1

Absent

absent from gnomAD v4.1

Conditions

hereditary neoplastic syndrome

Computational evidence

Protein change
AlphaMissense	0.8672	likely pathogenic
REVEL	0.361	indeterminate
SaProt	—	not scored · why
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 12	GERP 1.7, phastCons 1
Regional constraint	o/e 0.41	unconstrained · MANE · 9,812 bp · p 2.1e-34 · regional, not allelic
Overall
CADD	26.3	PHRED · no single calibrated threshold — expert panels disagree

AlphaMissense carries the ACMG weight for missense; REVEL is an independent agreement signal.

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: NF1
Protein: p.Arg2183Pro
Coding: c.6548G>C
MANE Select: NM_001042492
dbSNP: rs2069706142
Type: single nucleotide variant
Location: chr17:31337488 (GRCh38)
Gene constraint: LOEUF 0.449 · pLI 1.00 · ClinGen HI 3/3 (gnomAD)
Residue 2183: a turn

Full NF1 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: neurofibromatosis type 1

Similar variants

NF1 p.Arg2183Gln Uncertain significance ★★ same residue
NF1 p.Arg2183= Likely benign ★★ same residue
NF1 p.Arg2183Trp Uncertain significance ★ ⚠ same residue
NF1 p.Arg2183fs Pathogenic ★ same residue
NF1 c.1062+1G>A Pathogenic/Likely pathogenic ★★ same condition
NF1 c.1062+1G>C Pathogenic ★★ same condition
NF1 c.1062+2T>A Pathogenic/Likely pathogenic ★★ same condition
NF1 c.1062+2T>C Pathogenic/Likely 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/nf1-p-arg2183pro (accessed [today's date]).

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