Is NGF p.Arg83Cys (c.247C>T) pathogenic?

NGF p.Arg83Cys (c.247C>T) is classified Conflicting classifications of pathogenicity in NGF (ClinVar, Conflicting submitters, 10 submitters; last evaluated 2026-01-17). AlphaMissense: likely benign (0.1864); Ultra-rare (popmax 0.0465%, nfe); Associated with Inborn genetic diseases.

What condition is associated with NGF p.Arg83Cys (c.247C>T)?

NGF p.Arg83Cys (c.247C>T) is associated with Inborn genetic diseases, hereditary sensory and autonomic neuropathy type 5 (ClinVar).

How common is NGF p.Arg83Cys (c.247C>T) in the general population?

NGF p.Arg83Cys (c.247C>T) is ultra-rare (popmax 0.0465%, nfe) (gnomAD).

What do computational predictors say about NGF p.Arg83Cys (c.247C>T)?

AlphaMissense predicts likely benign (score 0.1864) — an in-silico prediction, not a clinical call.

NGF p.Arg83Cys

c.247C>T · rs138175552 · VCV245650

Conflicting classifications of pathogenicity Conflicting submitters

Classification

Conflicting classifications of pathogenicity

ClinVar

Review

Conflicting submitters ★☆☆☆

ClinVar · 10 submitters

AlphaMissense

likely benign

0.1864 · ACMG-weighted

gnomAD v4.1

Rare

ultra-rare (popmax 0.0465%, nfe)

Missense predictors

0/3 damaging

AlphaMissense, REVEL, SaProt

Conditions

Inborn genetic diseases

Computational evidence

Protein change
AlphaMissense	0.1864	likely benign
REVEL	0.286	benign-leaning
SaProt	LLR -8.57	tolerated
⇒ AlphaMissense, REVEL and SaProt all call this tolerated.
Splicing
SpliceAI	—	not looked up on this page · why
Constraint at this position
Conservation	phyloP 7.6	GERP 0.53, phastCons 1
Regional constraint	o/e 1.07	unconstrained · MANE · 299 bp · p 0.43 · regional, not allelic
Overall
CADD	26.5	PHRED · no single calibrated threshold — expert panels disagree

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

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.0465% European (non-Finnish) · 549/1,180,046 alleles

Filtering AF 0.0433% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.042%

Overall 0.0358% 578/1,614,208 alleles · ultra-rare

Ancestry group	Frequency	1 in
European (non-Finnish)grpmax	0.0465%	2,149
Middle Eastern	0.0165%	6,062
Remaining individualsnot grpmax-eligible	0.016%	6,251
Finnishnot grpmax-eligible	0.0141%	7,115
Ashkenazi Jewishnot grpmax-eligible	0.00676%	14,803
Admixed American	0.00333%	30,016
South Asian	0.00329%	30,361
African / African-American	0.00266%	37,528

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.Arg83Cys
Coding: c.247C>T
dbSNP: rs138175552
Type: single nucleotide variant
Location: chr1:115286549 (GRCh38)

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

Disease context

Inborn genetic diseases — disease report on Sugi Atlas → Associated genes, phenotypes, clinical trials & treatments

Also linked: hereditary sensory and autonomic neuropathy type 5

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-arg83cys (accessed [today's date]).

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