Is NF1 p.Ser82Phe (c.245C>T) pathogenic?

NF1 p.Ser82Phe (c.245C>T) is classified Pathogenic/Likely pathogenic in NF1 (ClinVar, Multiple submitters, 8 submitters; last evaluated 2026-03-10). AlphaMissense: likely pathogenic (0.9988); Very rare (popmax 0.00167%, amr); Associated with Cardiovascular phenotype.

What condition is associated with NF1 p.Ser82Phe (c.245C>T)?

NF1 p.Ser82Phe (c.245C>T) is associated with Cardiovascular phenotype, hereditary neoplastic syndrome, neurofibromatosis type 1 (ClinVar).

How common is NF1 p.Ser82Phe (c.245C>T) in the general population?

NF1 p.Ser82Phe (c.245C>T) is very rare (popmax 0.00167%, amr) (gnomAD).

What do computational predictors say about NF1 p.Ser82Phe (c.245C>T)?

AlphaMissense predicts likely pathogenic (score 0.9988) — an in-silico prediction, not a clinical call.

NF1 p.Ser82Phe

c.245C>T · rs199474729 · VCV68320

Pathogenic/Likely pathogenic Multiple submitters

Classification

Pathogenic/Likely pathogenic

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 8 submitters

AlphaMissense

likely pathogenic

0.9988 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 0.00167%, amr)

Conditions

Cardiovascular phenotype

Computational evidence

Protein change
AlphaMissense	0.9988	likely pathogenic ✓ concordant with ClinVar · top 4% in NF1
REVEL	0.595	indeterminate
SaProt	—	not scored · why
Splicing
SpliceAI	Δ0.74	acceptor gain · deltas
Pangolin	Δ0.69	gain · loss 0.45 · agrees with SpliceAI · independent
Constraint at this position
Conservation	phyloP 7.7	GERP 1.8, phastCons 1
Regional constraint	o/e 0.71	unconstrained · MANE · 87 kb · p 4.8e-08 · regional, not allelic
Overall
CADD	35.0	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 0.00167% Admixed American · 1/60,002 alleles

Overall 6.22e-05% 1/1,608,746 alleles · very rare exomes 1/1,456,510 · genomes 0/152,236 · 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.Ser82Phe
Coding: c.245C>T
MANE Select: NM_001042492
dbSNP: rs199474729
Type: single nucleotide variant
Location: chr17:31159050 (GRCh38)
Gene constraint: LOEUF 0.449 · pLI 1.00 · ClinGen HI 3/3 (gnomAD)
Residue 82: an α-helix; a UniProt-annotated variant site (in nf1)

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.Ser82Pro Pathogenic/Likely pathogenic ★★ same residue
NF1 p.Ser82= Likely benign ★★ same residue
NF1 p.Ser82Tyr Pathogenic ★ same residue
NF1 p.Ser82_Gln83insTer Pathogenic/Likely pathogenic ★★ same residue
NF1 p.Ser82_Ile85delinsGluArgAsp Likely pathogenic ★ same residue
NF1 p.Ser82fs Pathogenic ★ same residue
NF1 c.1062+1G>A Pathogenic/Likely pathogenic ★★ same condition
NF1 c.1062+1G>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-ser82phe (accessed [today's date]).

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