Is BDNF p.Glu168Ter (c.502G>T) pathogenic?

BDNF p.Glu168Ter (c.502G>T) is classified Likely pathogenic in BDNF (ClinVar, Single submitter, 1 submitter; last evaluated 2016-12-20). Absent from gnomAD v4.1; Associated with Inborn genetic diseases.

What condition is associated with BDNF p.Glu168Ter (c.502G>T)?

BDNF p.Glu168Ter (c.502G>T) is associated with Inborn genetic diseases (ClinVar).

How common is BDNF p.Glu168Ter (c.502G>T) in the general population?

BDNF p.Glu168Ter (c.502G>T) is absent from gnomAD v4.1 (gnomAD).

BDNF p.Glu168Ter

c.502G>T · rs1554931219 · VCV521383

Likely pathogenic Single submitter

Classification

Likely pathogenic

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

Consequence

nonsense (stop-gain)

predicted LoF

gnomAD v4.1

Absent

absent from gnomAD v4.1

Conditions

Inborn genetic diseases

Computational evidence

Protein change
Missense predictors do not apply to this variant type; conservation carries the signal.
Consequence	nonsense (stop-gain)	predicted loss-of-function in a LoF-intolerant gene
NMD	escapes	premature termination codon in the last exon (2 of 2) — the truncated protein is likely expressed. PVS1 input, not an applied code
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 7.7	GERP 2.9, phastCons 1
Overall
CADD	40.0	PHRED · no single calibrated threshold — expert panels disagree

Predicted loss-of-function is descriptive, not an applied PVS1 code.

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: BDNF
Protein: p.Glu168Ter
Coding: c.502G>T
MANE Select: NM_001709
dbSNP: rs1554931219
Type: single nucleotide variant
Location: chr11:27658063 (GRCh38)
Gene constraint: LOEUF 0.233 · pLI 1.00 (gnomAD)
Structure: AlphaFold pLDDT 71.44 · 2 PDB
Residue 168: a β-strand; a disulfide bond

Full BDNF 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

BDNF p.Asp86= Likely benign ★★ same condition
BDNF p.Thr149= Likely benign ★★ same condition
BDNF p.Ala24Thr Uncertain significance ★ ⚠ same condition
BDNF p.Ala51Val Uncertain significance ★ ⚠ same condition
BDNF p.Arg78Gln Uncertain significance ★ ⚠ same condition
BDNF p.Asp74Ala Uncertain significance ★ ⚠ same condition
BDNF p.Glu111Gln Uncertain significance ★ ⚠ same condition
BDNF p.Gly55Ser 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/bdnf-p-glu168ter (accessed [today's date]).

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