Is NGF p.Ala64Val (c.191C>T) pathogenic?

NGF p.Ala64Val (c.191C>T) is classified Conflicting classifications of pathogenicity in NGF (ClinVar, Conflicting submitters, 4 submitters; last evaluated 2025-12-08). AlphaMissense: likely benign (0.1011); Ultra-rare (popmax 0.0495%, mid); Associated with Inborn genetic diseases.

What condition is associated with NGF p.Ala64Val (c.191C>T)?

NGF p.Ala64Val (c.191C>T) is associated with Inborn genetic diseases, hereditary sensory and autonomic neuropathy type 5 (ClinVar).

How common is NGF p.Ala64Val (c.191C>T) in the general population?

NGF p.Ala64Val (c.191C>T) is ultra-rare (popmax 0.0495%, mid) (gnomAD).

What do computational predictors say about NGF p.Ala64Val (c.191C>T)?

AlphaMissense predicts likely benign (score 0.1011) — an in-silico prediction, not a clinical call.

NGF p.Ala64Val

c.191C>T · rs201087374 · VCV456628

Conflicting classifications of pathogenicity Conflicting submitters

Classification

Conflicting classifications of pathogenicity

ClinVar

Review

Conflicting submitters ★☆☆☆

ClinVar · 4 submitters

AlphaMissense

likely benign

0.1011 · ACMG-weighted

gnomAD v4.1

Rare

ultra-rare (popmax 0.0495%, mid)

Missense predictors

0/3 damaging

AlphaMissense, REVEL, SaProt

Conditions

Inborn genetic diseases

Computational evidence

Protein change
AlphaMissense	0.1011	likely benign
REVEL	0.097	moderately benign-leaning
SaProt	LLR -7.63	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 12	GERP 2.5, phastCons 1
Regional constraint	o/e 1.07	unconstrained · MANE · 299 bp · p 0.43 · regional, not allelic
Overall
CADD	19.94	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 0.0495% Middle Eastern · 3/6,060 alleles

Filtering AF 0.0223% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.0182%

Overall 0.00756% 122/1,614,180 alleles · ultra-rare

Ancestry group	Frequency	1 in
Remaining individualsnot grpmax-eligible	0.096%	1,042
Middle Easterngrpmax	0.0495%	2,020
East Asian	0.0357%	2,804
African / African-American	0.0266%	3,753
Admixed American	0.025%	4,002
South Asian	0.00329%	30,362
European (non-Finnish)	0.000424%	236,009

Remaining individuals shows a higher raw frequency than the grpmax group above it. gnomAD excludes bottlenecked groups — Finnish, Ashkenazi Jewish, Amish and “Remaining individuals” — from grpmax, because founder effects make their frequencies unrepresentative for filtering. The table is sorted by frequency, so an excluded group can sit above the grpmax row.

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.Ala64Val
Coding: c.191C>T
MANE Select: NM_002506
dbSNP: rs201087374
Type: single nucleotide variant
Location: chr1:115286605 (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-ala64val (accessed [today's date]).

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