Is NGF p.Arg95Ser (c.283C>A) pathogenic?

NGF p.Arg95Ser (c.283C>A) is classified Uncertain significance in NGF (ClinVar, Single submitter, 1 submitter; last evaluated 2018-01-12). AlphaMissense: likely benign (0.1099); Very rare (popmax 0.0022%, sas); Associated with hereditary sensory and autonomic neuropathy type 5.

What condition is associated with NGF p.Arg95Ser (c.283C>A)?

NGF p.Arg95Ser (c.283C>A) is associated with hereditary sensory and autonomic neuropathy type 5 (ClinVar).

How common is NGF p.Arg95Ser (c.283C>A) in the general population?

NGF p.Arg95Ser (c.283C>A) is very rare (popmax 0.0022%, sas) (gnomAD).

What do computational predictors say about NGF p.Arg95Ser (c.283C>A)?

AlphaMissense predicts likely benign (score 0.1099) — an in-silico prediction, not a clinical call.

NGF p.Arg95Ser

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.283C>A · rs771270154 · VCV875370

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.1099 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 0.0022%, sas)

Missense predictors

0/3 damaging

AlphaMissense, REVEL, SaProt

Conditions

hereditary sensory and autonomic neuropathy type 5

Computational evidence

Protein change
AlphaMissense	0.1099	likely benign
REVEL	0.13	moderately benign-leaning
SaProt	LLR -4.62	tolerated
⇒ AlphaMissense, REVEL and SaProt all call this tolerated.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 5.9	GERP 0.56, phastCons 1
Regional constraint	o/e 1.07	unconstrained · MANE · 299 bp · p 0.43 · regional, not allelic
Overall
CADD	8.787	PHRED · no single calibrated threshold — expert panels disagree

ClinVar classifies this uncertain; the computational predictors unanimously lean tolerated — a triage signal, not a reclassification

AlphaMissense carries the ACMG weight for missense; REVEL and SaProt are independent agreement signals.

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.0022% South Asian · 2/91,072 alleles

Filtering AF 0.000365% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.000137%

Overall 0.000496% 8/1,614,042 alleles · very rare

Ancestry group	Frequency	1 in
South Asiangrpmax	0.0022%	45,536
Remaining individualsnot grpmax-eligible	0.0016%	62,490
European (non-Finnish)	0.000424%	236,008

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.Arg95Ser
Coding: c.283C>A
MANE Select: NM_002506
dbSNP: rs771270154
Type: single nucleotide variant
Location: chr1:115286513 (GRCh38)
Gene constraint: LOEUF 0.67 · pLI 0.77 (gnomAD)
Structure: AlphaFold pLDDT 73.55 · 10 PDB

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.Arg95Cys Uncertain significance ★★ ⚠ same residue
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

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-arg95ser (accessed [today's date]).

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