Is NF1 p.Arg156= (c.468C>T) pathogenic?

NF1 p.Arg156= (c.468C>T) is classified Likely benign in NF1 (ClinVar, Multiple submitters, 2 submitters; last evaluated 2025-09-25). Very rare (popmax 0.00223%, eas); Associated with Cardiovascular phenotype.

What condition is associated with NF1 p.Arg156= (c.468C>T)?

NF1 p.Arg156= (c.468C>T) is associated with Cardiovascular phenotype, hereditary neoplastic syndrome, neurofibromatosis type 1 (ClinVar).

How common is NF1 p.Arg156= (c.468C>T) in the general population?

NF1 p.Arg156= (c.468C>T) is very rare (popmax 0.00223%, eas) (gnomAD).

NF1 p.Arg156=

c.468C>T · rs779074793 · VCV215715

Likely benign Multiple submitters

Classification

Likely benign

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 2 submitters

gnomAD v4.1

Rare

very rare (popmax 0.00223%, eas)

Conditions

Cardiovascular phenotype

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 -0.098	GERP -2.5, phastCons 0.32
Overall
CADD	5.428	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.00223% East Asian · 1/44,880 alleles

Filtering AF 0.000183% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.00012%

Overall 0.000434% 7/1,614,094 alleles · very rare exomes 7/1,461,784 · genomes 0/152,310 · joint denominator

Ancestry group	Frequency	1 in
East Asiangrpmax	0.00223%	44,880
European (non-Finnish)	0.000508%	196,663

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.Arg156=
Coding: c.468C>T
MANE Select: NM_001042492
dbSNP: rs779074793
Type: single nucleotide variant
Location: chr17:31163365 (GRCh38)
Gene constraint: LOEUF 0.449 · pLI 1.00 · ClinGen HI 3/3 (gnomAD)
Residue 156: an α-helix

Full NF1 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Disease context

Cardiovascular phenotype — disease report on Sugi Atlas → Associated genes, phenotypes, clinical trials & treatments

Also linked: hereditary neoplastic syndrome neurofibromatosis type 1

Similar variants

NF1 p.Arg156Cys Conflicting classifications of pathogenicity ★ ⚠ same residue
NF1 p.Arg156His Conflicting classifications of pathogenicity ★ ⚠ same residue
NF1 p.Arg156Leu Conflicting classifications of pathogenicity ★ ⚠ same residue
NF1 p.Arg156Pro Uncertain significance ★ ⚠ same residue
NF1 p.Arg156_Ile157insCysAsnAsnPheAsnAlaValPheSerArg Uncertain significance ★ 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

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-arg156 (accessed [today's date]).

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