Is NF1 p.Ile183= (c.549C>A) pathogenic?

NF1 p.Ile183= (c.549C>A) is classified Likely benign in NF1 (ClinVar, Multiple submitters, 2 submitters; last evaluated 2023-11-01). Ultra-rare (popmax 0.0194%, nfe); Associated with hereditary neoplastic syndrome.

What condition is associated with NF1 p.Ile183= (c.549C>A)?

NF1 p.Ile183= (c.549C>A) is associated with hereditary neoplastic syndrome (ClinVar).

How common is NF1 p.Ile183= (c.549C>A) in the general population?

NF1 p.Ile183= (c.549C>A) is ultra-rare (popmax 0.0194%, nfe) (gnomAD).

NF1 p.Ile183=

c.549C>A · rs1597643884 · VCV1747899

Likely benign Multiple submitters

Classification

Likely benign

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 2 submitters

gnomAD v4.1

Rare

ultra-rare (popmax 0.0194%, nfe)

Conditions

hereditary neoplastic syndrome

Computational evidence

Protein change
Missense predictors do not apply to this variant type; conservation carries the signal.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP -0.28	GERP -3.3, phastCons 0.21
Overall
CADD	4.275	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.0194% European (non-Finnish) · 190/979,864 alleles

Filtering AF 0.0171% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.0162%

Overall 0.0157% 215/1,366,150 alleles · ultra-rare exomes 215/1,215,218 · genomes 0/150,932 · joint denominator

Ancestry group	Frequency	1 in
European (non-Finnish)grpmax	0.0194%	5,157
Remaining individualsnot grpmax-eligible	0.0137%	7,273
Finnishnot grpmax-eligible	0.00933%	10,722
South Asian	0.00807%	12,384
Ashkenazi Jewishnot grpmax-eligible	0.00799%	12,523
Admixed American	0.00353%	28,339
African / African-American	0.00289%	34,654

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: NF1
Protein: p.Ile183=
Coding: c.549C>A
MANE Select: NM_001042492
dbSNP: rs1597643884
Type: single nucleotide variant
Location: chr17:31169960 (GRCh38)
Gene constraint: LOEUF 0.449 · pLI 1.00 · ClinGen HI 3/3 (gnomAD)

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

Similar variants

NF1 p.Ile183Met Uncertain significance ★★ same residue
NF1 p.Ile183Val Uncertain significance ★ same residue
NF1 p.Ile183Asn Conflicting classifications of pathogenicity ★ ⚠ same residue
NF1 c.1062+2T>C Pathogenic/Likely pathogenic ★★ same condition
NF1 c.1062+3A>G Pathogenic/Likely pathogenic ★★ same condition
NF1 c.1063-13G>A Pathogenic/Likely pathogenic ★★ same condition
NF1 c.1063-1G>A Pathogenic/Likely pathogenic ★★ same condition
NF1 c.1063-2A>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/nf1-p-ile183 (accessed [today's date]).

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