Is NGF p.Arg52Cys (c.154C>T) pathogenic?

NGF p.Arg52Cys (c.154C>T) is classified Uncertain significance in NGF (ClinVar, Multiple submitters, 4 submitters; last evaluated 2024-03-07). AlphaMissense: likely benign (0.1425); Very rare (popmax 0.00167%, amr); Associated with Inborn genetic diseases.

What condition is associated with NGF p.Arg52Cys (c.154C>T)?

NGF p.Arg52Cys (c.154C>T) is associated with Inborn genetic diseases, hereditary sensory and autonomic neuropathy type 5 (ClinVar).

How common is NGF p.Arg52Cys (c.154C>T) in the general population?

NGF p.Arg52Cys (c.154C>T) is very rare (popmax 0.00167%, amr) (gnomAD).

What do computational predictors say about NGF p.Arg52Cys (c.154C>T)?

AlphaMissense predicts likely benign (score 0.1425) — an in-silico prediction, not a clinical call.

NGF p.Arg52Cys

c.154C>T · rs766912679 · VCV645117

Uncertain significance Multiple submitters

Classification

Uncertain significance

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 4 submitters

AlphaMissense

likely benign

0.1425 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 0.00167%, amr)

Missense predictors

1/3 damaging

AlphaMissense, REVEL, SaProt

Conditions

Inborn genetic diseases

Computational evidence

Protein change
AlphaMissense	0.1425	likely benign
REVEL	0.14	moderately benign-leaning
SaProt	LLR -10.35	damaging
⇒ SaProt calls this damaging; AlphaMissense and REVEL do not.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 7.6	GERP 1.5, phastCons 1
Regional constraint	o/e 1.07	unconstrained · MANE · 299 bp · p 0.43 · regional, not allelic
Overall
CADD	23.5	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 0.00167% Admixed American · 1/60,012 alleles

Overall 0.000186% 3/1,614,116 alleles · very rare

Ancestry group	Frequency	1 in
Admixed Americangrpmax	0.00167%	60,012
South Asian	0.0011%	91,090
European (non-Finnish)	8.47e-05%	1,180,052

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.Arg52Cys
Coding: c.154C>T
MANE Select: NM_002506
dbSNP: rs766912679
Type: single nucleotide variant
Location: chr1:115286642 (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

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

Also linked: hereditary sensory and autonomic neuropathy type 5

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-arg52cys (accessed [today's date]).

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