Is BDNF p.Leu241= (c.721T>C) pathogenic?

BDNF p.Leu241= (c.721T>C) is classified Likely benign in BDNF (ClinVar, No assertion criteria, 1 submitter; last evaluated 2023-09-15). Very rare (popmax 0.000169%, nfe); Associated with BDNF-related disorder.

What condition is associated with BDNF p.Leu241= (c.721T>C)?

BDNF p.Leu241= (c.721T>C) is associated with BDNF-related disorder (ClinVar).

How common is BDNF p.Leu241= (c.721T>C) in the general population?

BDNF p.Leu241= (c.721T>C) is very rare (popmax 0.000169%, nfe) (gnomAD).

BDNF p.Leu241=

c.721T>C · VCV3356097

Likely benign No assertion criteria

Classification

Likely benign

ClinVar

Review

No assertion criteria ☆☆☆☆

ClinVar · 1 submitter

gnomAD v4.1

Rare

very rare (popmax 0.000169%, nfe)

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 0.88	GERP -5.8, phastCons 0.99
Overall
CADD	4.444	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.000169% European (non-Finnish) · 2/1,179,978 alleles

Filtering AF 2.8e-05% ClinGen BA1/BS1 input FAF95, joint · FAF99 1.1e-05%

Overall 0.000137% 2/1,461,830 alleles · very rare

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.Leu241=
Coding: c.721T>C
MANE Select: NM_001709
Type: single nucleotide variant
Location: chr11:27657844 (GRCh38)
Gene constraint: LOEUF 0.233 · pLI 1.00 (gnomAD)
Structure: AlphaFold pLDDT 71.44 · 2 PDB
Residue 241: a β-strand

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-leu241 (accessed [today's date]).

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