Is NF1 p.Pro268= (c.804A>G) pathogenic?

NF1 p.Pro268= (c.804A>G) is classified Likely benign in NF1 (ClinVar, Multiple submitters, 2 submitters; last evaluated 2023-10-22). Very rare (popmax 0.00549%, sas); Associated with Cardiovascular phenotype.

What condition is associated with NF1 p.Pro268= (c.804A>G)?

NF1 p.Pro268= (c.804A>G) is associated with Cardiovascular phenotype, hereditary neoplastic syndrome, neurofibromatosis type 1 (ClinVar).

How common is NF1 p.Pro268= (c.804A>G) in the general population?

NF1 p.Pro268= (c.804A>G) is very rare (popmax 0.00549%, sas) (gnomAD).

NF1 p.Pro268=

c.804A>G · rs759964997 · VCV457866

Likely benign Multiple submitters

Classification

Likely benign

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 2 submitters

gnomAD v4.1

Rare

very rare (popmax 0.00549%, sas)

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 -1.5	GERP -3.6
Overall
CADD	4.028	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.00549% South Asian · 5/91,062 alleles

Filtering AF 0.0021% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.00136%

Overall 0.00031% 5/1,613,954 alleles · very rare exomes 4/1,461,710 · genomes 1/152,244 · joint denominator

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.Pro268=
Coding: c.804A>G
MANE Select: NM_001042492
dbSNP: rs759964997
Type: single nucleotide variant
Location: chr17:31182581 (GRCh38)
Gene constraint: LOEUF 0.449 · pLI 1.00 · ClinGen HI 3/3 (gnomAD)
Residue 268: 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.Pro268Gln Uncertain significance ★★ ⚠ same residue
NF1 p.Pro268Leu Uncertain significance ★★ ⚠ same residue
NF1 p.Pro268Arg 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
NF1 c.1062+2T>C Pathogenic/Likely pathogenic ★★ same condition
NF1 c.1062+3A>G 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-pro268 (accessed [today's date]).

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