Is BDNF p.Ser45= (c.135C>T) pathogenic?

BDNF p.Ser45= (c.135C>T) is classified Likely benign in BDNF (ClinVar, No assertion criteria, 1 submitter; last evaluated 2021-09-14). Ultra-rare (popmax 0.0253%, sas); Associated with BDNF-related disorder.

What condition is associated with BDNF p.Ser45= (c.135C>T)?

BDNF p.Ser45= (c.135C>T) is associated with BDNF-related disorder (ClinVar).

How common is BDNF p.Ser45= (c.135C>T) in the general population?

BDNF p.Ser45= (c.135C>T) is ultra-rare (popmax 0.0253%, sas) (gnomAD).

BDNF p.Ser45=

c.135C>T · rs747701929 · VCV3060439

Likely benign No assertion criteria

Classification

Likely benign

ClinVar

Review

No assertion criteria ☆☆☆☆

ClinVar · 1 submitter

gnomAD v4.1

Rare

ultra-rare (popmax 0.0253%, sas)

Conditions

BDNF-related disorder

Computational evidence

Protein change
Missense predictors do not apply to this variant type; conservation carries the signal.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 2.9	GERP -0.91, phastCons 1
Overall
CADD	15.96	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.0253% South Asian · 23/91,088 alleles

Filtering AF 0.0172% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.0146%

Overall 0.00186% 30/1,614,066 alleles · ultra-rare exomes 28/1,461,878 · genomes 2/152,188 · joint denominator

Ancestry group	Frequency	1 in
South Asiangrpmax	0.0253%	3,960
East Asian	0.00223%	44,884
Remaining individualsnot grpmax-eligible	0.0016%	62,490
African / African-American	0.00133%	74,926
European (non-Finnish)	0.000339%	295,015

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: BDNF
Protein: p.Ser45=
Coding: c.135C>T
MANE Select: NM_001709
dbSNP: rs747701929
Type: single nucleotide variant
Location: chr11:27658430 (GRCh38)
Gene constraint: LOEUF 0.233 · pLI 1.00 (gnomAD)
Structure: AlphaFold pLDDT 71.44 · 2 PDB

Full BDNF gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Disease context

BDNF-related disorder

Similar variants

BDNF c.-21-15487T>G Uncertain significance ★ same condition
BDNF c.-21-15496C>G Uncertain significance ★ same condition
BDNF p.Arg38Gln Uncertain significance ★ ⚠ same condition
BDNF p.Gly31Asp Uncertain significance ★ ⚠ same condition
BDNF p.Lys76Glu Uncertain significance ★ ⚠ same condition
BDNF p.Met220Thr Uncertain significance ★ same condition
BDNF c.-21-15481C>A Uncertain significance same condition
BDNF c.-21-15533T>C 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-ser45 (accessed [today's date]).

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