Is NGF p.Phe113Ser (c.338T>C) pathogenic?

NGF p.Phe113Ser (c.338T>C) is classified Uncertain significance in NGF (ClinVar, Single submitter, 1 submitter; last evaluated 2022-06-16). AlphaMissense: likely benign (0.0665); Absent from gnomAD v4.1; Associated with hereditary sensory and autonomic neuropathy type 5.

What condition is associated with NGF p.Phe113Ser (c.338T>C)?

NGF p.Phe113Ser (c.338T>C) is associated with hereditary sensory and autonomic neuropathy type 5 (ClinVar).

How common is NGF p.Phe113Ser (c.338T>C) in the general population?

NGF p.Phe113Ser (c.338T>C) is absent from gnomAD v4.1 (gnomAD).

What do computational predictors say about NGF p.Phe113Ser (c.338T>C)?

AlphaMissense predicts likely benign (score 0.0665) — an in-silico prediction, not a clinical call.

NGF p.Phe113Ser

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.338T>C · rs2525330638 · VCV2118913

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.0665 · ACMG-weighted

gnomAD v4.1

Absent

absent from gnomAD v4.1

Missense predictors

0/3 damaging

AlphaMissense, REVEL, SaProt

Conditions

hereditary sensory and autonomic neuropathy type 5

Computational evidence

Protein change
AlphaMissense	0.0665	likely benign
REVEL	0.035	moderately benign-leaning
SaProt	LLR -4.10	tolerated
⇒ AlphaMissense, REVEL and SaProt all call this tolerated.
Splicing
SpliceAI	—	not looked up on this page · why
Constraint at this position
Conservation	phyloP 1.3	GERP -5, phastCons 0.073
Regional constraint	o/e 0.70	unconstrained · MANE · 422 bp · p 3.2e-05 · regional, not allelic
Overall
CADD	8.534	PHRED · no single calibrated threshold — expert panels disagree

ClinVar classifies this uncertain; the computational predictors unanimously lean tolerated — 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.Phe113Ser
Coding: c.338T>C
dbSNP: rs2525330638
Type: single nucleotide variant
Location: chr1:115286458 (GRCh38)

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)

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-phe113ser (accessed [today's date]).

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