Is NGF p.Ala18= (c.54G>A) pathogenic?

NGF p.Ala18= (c.54G>A) is classified Benign in NGF (ClinVar, Multiple submitters, 7 submitters; last evaluated 2026-02-02). Common (popmax 13.2%, afr) — too common for a highly-penetrant pathogenic allele; Associated with hereditary sensory and autonomic neuropathy type 5.

What condition is associated with NGF p.Ala18= (c.54G>A)?

NGF p.Ala18= (c.54G>A) is associated with hereditary sensory and autonomic neuropathy type 5 (ClinVar).

NGF p.Ala18=

Q: How common is NGF p.Ala18= (c.54G>A) in the general population?

NGF p.Ala18= (c.54G>A) is common (popmax 13.2%, afr) — too common for a highly-penetrant pathogenic allele (gnomAD).

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.54G>A · rs6325 · VCV291994

Benign Multiple submitters

Classification

Benign

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 7 submitters

gnomAD v4.1

Common

common (popmax 13.2%, afr) — too common for a highly-penetrant pathogenic allele

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 0.47	GERP -3.3, phastCons 1
Overall
CADD	11.75	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 13.2% African / African-American · 9,898/75,000 alleles

Filtering AF 13% ClinGen BA1/BS1 input FAF95, joint · FAF99 12.9%

Overall 0.693% 11,186/1,614,086 alleles · common

Ancestry group	Frequency	1 in
African / African-Americangrpmax	13.2%	8
Remaining individualsnot grpmax-eligible	0.84%	119
Admixed American	0.798%	125
Middle Eastern	0.561%	178
South Asian	0.0417%	2,397
European (non-Finnish)	0.018%	5,566

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.Ala18=
Coding: c.54G>A
MANE Select: NM_002506
dbSNP: rs6325
Type: single nucleotide variant
Location: chr1:115286742 (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.Ala18Val Uncertain significance ★★ ⚠ same residue
NGF p.Arg221Trp Likely pathogenic ★★ same condition
NGF p.Ala11Thr 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-ala18 (accessed [today's date]).

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