Is NGF p.Ser168Arg (c.504T>A) pathogenic?

NGF p.Ser168Arg (c.504T>A) is classified Uncertain significance in NGF (ClinVar, Single submitter, 1 submitter; last evaluated 2019-07-08). AlphaMissense: ambiguous (0.3906); Absent from gnomAD v4.1.

How common is NGF p.Ser168Arg (c.504T>A) in the general population?

NGF p.Ser168Arg (c.504T>A) is absent from gnomAD v4.1 (gnomAD).

What do computational predictors say about NGF p.Ser168Arg (c.504T>A)?

AlphaMissense predicts ambiguous (score 0.3906) — an in-silico prediction, not a clinical call.

NGF p.Ser168Arg

c.504T>A · rs745359909 · VCV1302230

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

ambiguous

0.3906 · ACMG-weighted

gnomAD v4.1

Absent

absent from gnomAD v4.1

Missense predictors

0/2 damaging

REVEL, SaProt · AlphaMissense no call

Computational evidence

Protein change
AlphaMissense	0.3906	ambiguous
REVEL	0.109	moderately benign-leaning
SaProt	LLR -5.75	tolerated
⇒ REVEL and SaProt both call this tolerated; AlphaMissense makes no call.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP -1.4	GERP -4.9
Regional constraint	o/e 0.70	unconstrained · MANE · 422 bp · p 3.2e-05 · regional, not allelic
Overall
CADD	12.84	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

Absent from gnomAD v4.1. Not observed in any sequenced alleles — a rarity signal (ACMG PM2-supporting), not evidence of pathogenicity on its own.

Variant & gene context

Gene: NGF
Protein: p.Ser168Arg
Coding: c.504T>A
MANE Select: NM_002506
dbSNP: rs745359909
Type: single nucleotide variant
Location: chr1:115286292 (GRCh38)
Gene constraint: LOEUF 0.67 · pLI 0.77 (gnomAD)
Structure: AlphaFold pLDDT 73.55 · 10 PDB
Residue 168: a β-strand; a disulfide bond

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

Similar variants

NGF p.Arg221Trp Likely pathogenic ★★ same type
NGF p.Ala11Thr Uncertain significance ★★ ⚠ same type
NGF p.Ala18Val Uncertain significance ★★ ⚠ same type
NGF p.Ala54Thr Uncertain significance ★★ ⚠ same type
NGF p.Arg121Trp Uncertain significance ★★ ⚠ same type
NGF p.Arg130Gly Uncertain significance ★★ ⚠ same type
NGF p.Arg180Gln Uncertain significance ★★ ⚠ same type
NGF p.Arg49Cys Uncertain significance ★★ ⚠ same type

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-ser168arg (accessed [today's date]).

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