Is NGF p.Phe89Leu (c.265T>C) pathogenic?

NGF p.Phe89Leu (c.265T>C) is classified Uncertain significance in NGF (ClinVar, Single submitter, 1 submitter; last evaluated 2025-01-14). AlphaMissense: likely pathogenic (0.9733); Ultra-rare (popmax 0.0133%, amr); Associated with Inborn genetic diseases.

What condition is associated with NGF p.Phe89Leu (c.265T>C)?

NGF p.Phe89Leu (c.265T>C) is associated with Inborn genetic diseases (ClinVar).

How common is NGF p.Phe89Leu (c.265T>C) in the general population?

NGF p.Phe89Leu (c.265T>C) is ultra-rare (popmax 0.0133%, amr) (gnomAD).

What do computational predictors say about NGF p.Phe89Leu (c.265T>C)?

AlphaMissense predicts likely pathogenic (score 0.9733) — an in-silico prediction, not a clinical call.

NGF p.Phe89Leu

c.265T>C · VCV3879391

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely pathogenic

0.9733 · ACMG-weighted

gnomAD v4.1

Rare

ultra-rare (popmax 0.0133%, amr)

Missense predictors

1/3 damaging

AlphaMissense, REVEL, SaProt

Conditions

Inborn genetic diseases

Computational evidence

Protein change
AlphaMissense	0.9733	likely pathogenic · top 10% in NGF
REVEL	0.267	benign-leaning
SaProt	LLR -7.35	tolerated
⇒ AlphaMissense calls this damaging; REVEL and SaProt do not.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 9.4	GERP 1.5, phastCons 1
Regional constraint	o/e 1.07	unconstrained · MANE · 299 bp · p 0.43 · regional, not allelic
Overall
CADD	22.0	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 0.0133% Admixed American · 8/60,018 alleles

Filtering AF 0.00661% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.00482%

Overall 0.000496% 8/1,614,190 alleles · ultra-rare exomes 8/1,461,886 · genomes 0/152,304 · joint denominator

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.Phe89Leu
Coding: c.265T>C
MANE Select: NM_002506
Type: single nucleotide variant
Location: chr1:115286531 (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

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NGF p.Arg68Cys Uncertain significance ★★ ⚠ same condition
NGF p.Arg86His 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-phe89leu (accessed [today's date]).

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