Is BDNF p.Ser139Arg (c.417C>A) pathogenic?

BDNF p.Ser139Arg (c.417C>A) is classified Uncertain significance in BDNF (ClinVar, Single submitter, 1 submitter; last evaluated 2025-06-30). AlphaMissense: likely pathogenic (0.9992); Absent from gnomAD v4.1; Associated with Inborn genetic diseases.

What condition is associated with BDNF p.Ser139Arg (c.417C>A)?

BDNF p.Ser139Arg (c.417C>A) is associated with Inborn genetic diseases (ClinVar).

How common is BDNF p.Ser139Arg (c.417C>A) in the general population?

BDNF p.Ser139Arg (c.417C>A) is absent from gnomAD v4.1 (gnomAD).

What do computational predictors say about BDNF p.Ser139Arg (c.417C>A)?

AlphaMissense predicts likely pathogenic (score 0.9992) — an in-silico prediction, not a clinical call.

BDNF p.Ser139Arg

c.417C>A · VCV4204037

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely pathogenic

0.9992 · 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	0.9992	likely pathogenic · top 4% in BDNF
REVEL	0.723	pathogenic-leaning
SaProt	LLR -14.06	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 0.68	GERP -1.4, phastCons 1
Regional constraint	o/e 0.44	unconstrained · MANE · 364 bp · p 6.8e-13 · regional, not allelic
Overall
CADD	23.7	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: BDNF
Protein: p.Ser139Arg
Coding: c.417C>A
MANE Select: NM_001709
Type: single nucleotide variant
Location: chr11:27658148 (GRCh38)
Gene constraint: LOEUF 0.233 · pLI 1.00 (gnomAD)
Structure: AlphaFold pLDDT 71.44 · 2 PDB
Residue 139: a β-strand

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.Ser139= Likely benign ★ same residue
BDNF p.Asp86= Likely benign ★★ same condition
BDNF p.Thr149= Likely benign ★★ same condition
BDNF p.Glu168Ter Likely pathogenic ★ 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

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-ser139arg (accessed [today's date]).

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