Is NGF p.Ser140= (c.420C>T) pathogenic?

NGF p.Ser140= (c.420C>T) is classified Likely benign in NGF (ClinVar, Single submitter, 1 submitter; last evaluated 2024-04-30). Ultra-rare (popmax 0.0134%, afr); Associated with hereditary sensory and autonomic neuropathy type 5.

What condition is associated with NGF p.Ser140= (c.420C>T)?

NGF p.Ser140= (c.420C>T) is associated with hereditary sensory and autonomic neuropathy type 5 (ClinVar).

How common is NGF p.Ser140= (c.420C>T) in the general population?

NGF p.Ser140= (c.420C>T) is ultra-rare (popmax 0.0134%, afr) (gnomAD).

NGF p.Ser140=

Q: How is Hereditary sensory and autonomic neuropathy type 5 inherited?

Typically Autosomal recessive (Orphanet). A genetic counselor can assess individual risk for a family.

c.420C>T · rs751386981 · VCV1494796

Likely benign Single submitter

Classification

Likely benign

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

gnomAD v4.1

Rare

ultra-rare (popmax 0.0134%, afr)

Conditions

hereditary sensory and autonomic neuropathy type 5

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 0.041	GERP -0.42, phastCons 0.43
Overall
CADD	9.586	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.0134% African / African-American · 10/74,848 alleles

Filtering AF 0.00724% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.0055%

Overall 0.00093% 15/1,613,760 alleles · ultra-rare

Ancestry group	Frequency	1 in
African / African-Americangrpmax	0.0134%	7,485
European (non-Finnish)	0.000424%	235,997

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: NGF
Protein: p.Ser140=
Coding: c.420C>T
MANE Select: NM_002506
dbSNP: rs751386981
Type: single nucleotide variant
Location: chr1:115286376 (GRCh38)
Gene constraint: LOEUF 0.67 · pLI 0.77 (gnomAD)
Structure: AlphaFold pLDDT 73.55 · 10 PDB
Residue 140: a β-strand; a disulfide bond

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

Disease context

hereditary sensory and autonomic neuropathy type 5 — disease report on Sugi Atlas → Associated genes, phenotypes, clinical trials & treatments

For Hereditary sensory and autonomic neuropathy type 5 (Orphanet):

Inheritance: Autosomal recessive
Onset: Infancy, Neonatal
Prevalence: <1 / 1 000 000 (Europe)

Similar variants

NGF p.Arg221Trp Likely pathogenic ★★ same condition
NGF p.Ala11Thr Uncertain significance ★★ ⚠ same condition
NGF p.Ala18Val Uncertain significance ★★ ⚠ same condition
NGF p.Ala54Thr Uncertain significance ★★ ⚠ same condition
NGF p.Arg121Trp Uncertain significance ★★ ⚠ same condition
NGF p.Arg130Gly Uncertain significance ★★ ⚠ same condition
NGF p.Arg180Gln Uncertain significance ★★ ⚠ same condition
NGF p.Arg49Cys Uncertain significance ★★ ⚠ 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/ngf-p-ser140 (accessed [today's date]).

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