Is NGF p.Arg86Pro (c.257G>C) pathogenic?

NGF p.Arg86Pro (c.257G>C) is classified Uncertain significance in NGF (ClinVar, Single submitter, 1 submitter; last evaluated 2021-01-12). AlphaMissense: likely pathogenic (0.9741); Absent from gnomAD v4.1; Associated with Inborn genetic diseases.

What condition is associated with NGF p.Arg86Pro (c.257G>C)?

NGF p.Arg86Pro (c.257G>C) is associated with Inborn genetic diseases (ClinVar).

How common is NGF p.Arg86Pro (c.257G>C) in the general population?

NGF p.Arg86Pro (c.257G>C) is absent from gnomAD v4.1 (gnomAD).

What do computational predictors say about NGF p.Arg86Pro (c.257G>C)?

AlphaMissense predicts likely pathogenic (score 0.9741) — an in-silico prediction, not a clinical call.

NGF p.Arg86Pro

c.257G>C · rs200629339 · VCV1793360

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely pathogenic

0.9741 · ACMG-weighted

gnomAD v4.1

Absent

absent from gnomAD v4.1

Missense predictors

3/3 damaging

AlphaMissense, REVEL, SaProt

Conditions

Inborn genetic diseases

Computational evidence

Protein change
AlphaMissense	0.9741	likely pathogenic · top 10% in NGF
REVEL	0.904	moderately pathogenic-leaning
SaProt	LLR -13.91	damaging
⇒ AlphaMissense, REVEL and SaProt all call this damaging.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 7.7	GERP 1.6, phastCons 1
Regional constraint	o/e 1.07	unconstrained · MANE · 299 bp · p 0.43 · regional, not allelic
Overall
CADD	25.9	PHRED · no single calibrated threshold — expert panels disagree

ClinVar classifies this uncertain; the computational predictors unanimously lean damaging — a triage signal, not a reclassification

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.Arg86Pro
Coding: c.257G>C
MANE Select: NM_002506
dbSNP: rs200629339
Type: single nucleotide variant
Location: chr1:115286539 (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

Similar variants

NGF p.Arg86His Uncertain significance ★★ ⚠ same residue
NGF p.Arg49His Uncertain significance ★★ ⚠ same condition
NGF p.Arg52Cys Uncertain significance ★★ ⚠ same condition
NGF p.Arg62His Uncertain significance ★★ ⚠ same condition
NGF p.Arg68Cys Uncertain significance ★★ ⚠ same condition
NGF p.Asp45Asn Uncertain significance ★★ ⚠ same condition
NGF p.Gln66Lys Uncertain significance ★★ ⚠ same condition
NGF p.Gly188Arg 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-arg86pro (accessed [today's date]).

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