Is BDNF p.Ala17Thr (c.49G>A) pathogenic?

BDNF p.Ala17Thr (c.49G>A) is classified Uncertain significance in BDNF (ClinVar, No assertion criteria, 1 submitter; last evaluated 2024-09-16). Ultra-rare (popmax 0.0651%, afr); Associated with BDNF-related disorder.

What condition is associated with BDNF p.Ala17Thr (c.49G>A)?

BDNF p.Ala17Thr (c.49G>A) is associated with BDNF-related disorder (ClinVar).

How common is BDNF p.Ala17Thr (c.49G>A) in the general population?

BDNF p.Ala17Thr (c.49G>A) is ultra-rare (popmax 0.0651%, afr) (gnomAD).

BDNF p.Ala17Thr

c.49G>A · rs377250764 · VCV2635757

Uncertain significance No assertion criteria

Classification

Uncertain significance

ClinVar

Review

No assertion criteria ☆☆☆☆

ClinVar · 1 submitter

gnomAD v4.1

Rare

ultra-rare (popmax 0.0651%, afr)

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 4.5	GERP 1.2, phastCons 1
Overall
CADD	16.49	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.0651% African / African-American · 44/67,624 alleles

Filtering AF 0.0497% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.0444%

Overall 0.00331% 45/1,361,382 alleles · ultra-rare

Ancestry group	Frequency	1 in
African / African-Americangrpmax	0.0651%	1,537
Admixed American	0.00193%	51,914

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.Ala17Thr
Coding: c.49G>A
MANE Select: NM_001709 · reported on NM_001143809
dbSNP: rs377250764
Type: single nucleotide variant
Location: chr11:27700988 (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 p.Lys17Glu Uncertain significance ★ ⚠ same residue
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

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-ala17thr (accessed [today's date]).

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