Is BDNF p.Thr149= (c.447G>A) pathogenic?

BDNF p.Thr149= (c.447G>A) is classified Likely benign in BDNF (ClinVar, Multiple submitters, 3 submitters; last evaluated 2023-08-04). Ultra-rare (popmax 0.066%, mid); Associated with Inborn genetic diseases.

What condition is associated with BDNF p.Thr149= (c.447G>A)?

BDNF p.Thr149= (c.447G>A) is associated with Inborn genetic diseases (ClinVar).

How common is BDNF p.Thr149= (c.447G>A) in the general population?

BDNF p.Thr149= (c.447G>A) is ultra-rare (popmax 0.066%, mid) (gnomAD).

BDNF p.Thr149=

c.447G>A · rs144235869 · VCV2309743

Likely benign Multiple submitters

Classification

Likely benign

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 3 submitters

gnomAD v4.1

Rare

ultra-rare (popmax 0.066%, mid)

Conditions

Inborn genetic diseases

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 -7.9	GERP -5.8
Overall
CADD	0.134	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.066% Middle Eastern · 4/6,062 alleles

Filtering AF 0.0248% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.0209%

Overall 0.0183% 295/1,614,114 alleles · ultra-rare

Ancestry group	Frequency	1 in
Middle Easterngrpmax	0.066%	1,516
Admixed American	0.0367%	2,728
Remaining individualsnot grpmax-eligible	0.0256%	3,907
European (non-Finnish)	0.0204%	4,896
African / African-American	0.0107%	9,376
Finnishnot grpmax-eligible	0.00312%	32,016
South Asian	0.0022%	45,536

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.Thr149=
Coding: c.447G>A
MANE Select: NM_001709
dbSNP: rs144235869
Type: single nucleotide variant
Location: chr11:27658118 (GRCh38)
Gene constraint: LOEUF 0.233 · pLI 1.00 (gnomAD)
Structure: AlphaFold pLDDT 71.44 · 2 PDB
Residue 149: 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.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
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-thr149 (accessed [today's date]).

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