Is NGF p.Ala58Val (c.173C>T) pathogenic?

NGF p.Ala58Val (c.173C>T) is classified Benign/Likely benign in NGF (ClinVar, Multiple submitters, 6 submitters; last evaluated 2025-08-11). AlphaMissense: likely benign (0.092); Rare (popmax 0.818%, sas); Associated with Inborn genetic diseases.

What condition is associated with NGF p.Ala58Val (c.173C>T)?

NGF p.Ala58Val (c.173C>T) is associated with Inborn genetic diseases, hereditary sensory and autonomic neuropathy type 5 (ClinVar).

How common is NGF p.Ala58Val (c.173C>T) in the general population?

NGF p.Ala58Val (c.173C>T) is rare (popmax 0.818%, sas) (gnomAD).

What do computational predictors say about NGF p.Ala58Val (c.173C>T)?

AlphaMissense predicts likely benign (score 0.092) — an in-silico prediction, not a clinical call.

NGF p.Ala58Val

c.173C>T · rs201861727 · VCV456627

Benign/Likely benign Multiple submitters

Classification

Benign/Likely benign

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 6 submitters

AlphaMissense

likely benign

0.092 · ACMG-weighted

gnomAD v4.1

Rare

rare (popmax 0.818%, sas)

Missense predictors

0/3 damaging

AlphaMissense, REVEL, SaProt

Conditions

Inborn genetic diseases

Computational evidence

Protein change
AlphaMissense	0.092	likely benign
REVEL	0.098	moderately benign-leaning
SaProt	LLR -7.14	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 4.4	GERP -2.6, phastCons 0.89
Regional constraint	o/e 1.07	unconstrained · MANE · 299 bp · p 0.43 · regional, not allelic
Overall
CADD	12.16	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 0.818% South Asian · 745/91,088 alleles

Filtering AF 0.769% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.75%

Overall 0.0501% 808/1,614,214 alleles · rare exomes 758/1,461,876 · genomes 50/152,338 · joint denominator

Ancestry group	Frequency	1 in
South Asiangrpmax	0.818%	122
Remaining individualsnot grpmax-eligible	0.056%	1,786
East Asian	0.00223%	44,876
European (non-Finnish)	0.0022%	45,386
African / African-American	0.00133%	75,056

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.Ala58Val
Coding: c.173C>T
MANE Select: NM_002506
dbSNP: rs201861727
Type: single nucleotide variant
Location: chr1:115286623 (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.Ala58= Conflicting classifications of pathogenicity ★ same residue
NGF p.Ala58Ser 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

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-ala58val (accessed [today's date]).

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