Is NF1 p.Ala797Val (c.2390C>T) pathogenic?

NF1 p.Ala797Val (c.2390C>T) is classified Conflicting classifications of pathogenicity in NF1 (ClinVar, Conflicting submitters, 4 submitters; last evaluated 2024-09-05). AlphaMissense: likely benign (0.0948); Very rare (popmax 0.00223%, eas); Associated with Cardiovascular phenotype.

What condition is associated with NF1 p.Ala797Val (c.2390C>T)?

NF1 p.Ala797Val (c.2390C>T) is associated with Cardiovascular phenotype, hereditary neoplastic syndrome, neurofibromatosis type 1 (ClinVar).

How common is NF1 p.Ala797Val (c.2390C>T) in the general population?

NF1 p.Ala797Val (c.2390C>T) is very rare (popmax 0.00223%, eas) (gnomAD).

What do computational predictors say about NF1 p.Ala797Val (c.2390C>T)?

AlphaMissense predicts likely benign (score 0.0948) — an in-silico prediction, not a clinical call.

NF1 p.Ala797Val

c.2390C>T · rs1181350360 · VCV481943

Conflicting classifications of pathogenicity Conflicting submitters

Classification

Conflicting classifications of pathogenicity

ClinVar

Review

Conflicting submitters ★☆☆☆

ClinVar · 4 submitters

AlphaMissense

likely benign

0.0948 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 0.00223%, eas)

Missense predictors

0/2 damaging

AlphaMissense, REVEL · SaProt no call

Conditions

Cardiovascular phenotype

Computational evidence

Protein change
AlphaMissense	0.0948	likely benign
REVEL	0.041	moderately benign-leaning
SaProt	—	not scored · why
⇒ AlphaMissense and REVEL both call this tolerated; SaProt makes no call.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 4.1	GERP -0.2, phastCons 1
Regional constraint	o/e 0.59	unconstrained · MANE · 7,685 bp · p 1.1e-24 · regional, not allelic
Overall
CADD	22.3	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

Grpmax group 0.00223% East Asian · 1/44,852 alleles

Filtering AF 2.8e-05% ClinGen BA1/BS1 input FAF95, joint · FAF99 1.1e-05%

Overall 0.000186% 3/1,613,708 alleles · very rare exomes 3/1,461,476 · genomes 0/152,232 · joint denominator

Ancestry group	Frequency	1 in
East Asiangrpmax	0.00223%	44,852
European (non-Finnish)	0.00017%	589,887

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.Ala797Val
Coding: c.2390C>T
MANE Select: NM_001042492
dbSNP: rs1181350360
Type: single nucleotide variant
Location: chr17:31227587 (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

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.Ala797= Likely benign ★★ same residue
NF1 p.Ala797Thr Likely benign ★ same residue
NF1 p.Ala797fs 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
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-ala797val (accessed [today's date]).

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