Is NTRK2 p.Pro810= (c.2430C>T) pathogenic?

NTRK2 p.Pro810= (c.2430C>T) is classified Benign/Likely benign in NTRK2 (ClinVar, Multiple submitters, 5 submitters; last evaluated 2026-02-03). Low-frequency (popmax 4.22%, amr); Associated with obesity, hyperphagia, and developmental delay.

What condition is associated with NTRK2 p.Pro810= (c.2430C>T)?

NTRK2 p.Pro810= (c.2430C>T) is associated with obesity, hyperphagia, and developmental delay, developmental and epileptic encephalopathy, 58 (ClinVar).

How common is NTRK2 p.Pro810= (c.2430C>T) in the general population?

NTRK2 p.Pro810= (c.2430C>T) is low-frequency (popmax 4.22%, amr) (gnomAD).

NTRK2 p.Pro810=

Q: How is Early-onset obesity-hyperphagia-severe developmental delay syndrome inherited?

Typically Autosomal dominant (Orphanet). A genetic counselor can assess individual risk for a family.

c.2430C>T · rs56142442 · VCV285975

Benign/Likely benign Multiple submitters

Classification

Benign/Likely benign

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 5 submitters

gnomAD v4.1

Rare

low-frequency (popmax 4.22%, amr)

Conditions

obesity, hyperphagia, and developmental delay

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 -0.34	GERP -1.1, phastCons 0.061
Overall
CADD	5.522	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 4.22% Admixed American · 2,532/60,024 alleles

Filtering AF 4.08% ClinGen BA1/BS1 input FAF95, joint · FAF99 4.03%

Overall 0.171% 2,764/1,614,132 alleles · low-frequency exomes 2,412/1,461,882 · genomes 352/152,250 · joint denominator

Ancestry group	Frequency	1 in
Admixed Americangrpmax	4.22%	24
Remaining individualsnot grpmax-eligible	0.155%	644
African / African-American	0.0706%	1,416
Middle Eastern	0.0165%	6,062
South Asian	0.011%	9,108
European (non-Finnish)	0.00593%	16,857
Finnishnot grpmax-eligible	0.00156%	64,036

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: NTRK2
Protein: p.Pro810=
Coding: c.2430C>T
MANE Select: NM_006180
dbSNP: rs56142442
Type: single nucleotide variant
Location: chr9:85021350 (GRCh38)
Gene constraint: LOEUF 0.123 · pLI 1.00 (gnomAD)
Structure: AlphaFold pLDDT 77.53 · 9 PDB
Residue 810: an α-helix; a UniProt-annotated variant site (in obhd)

Full NTRK2 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Disease context

obesity, hyperphagia, and developmental delay — disease report on Sugi Atlas → Associated genes, phenotypes, clinical trials & treatments

Also linked: developmental and epileptic encephalopathy, 58

For Early-onset obesity-hyperphagia-severe developmental delay syndrome (Orphanet):

Inheritance: Autosomal dominant

Similar variants

NTRK2 p.Pro810Arg Uncertain significance ★ ⚠ same residue
NTRK2 p.Arg551Gln Likely pathogenic ★★ same condition
NTRK2 p.Tyr434Cys Pathogenic/Likely pathogenic ★★ ⚠ same condition
NTRK2 p.Ala440Val Uncertain significance ★★ ⚠ same condition
NTRK2 p.Arg790Ter Uncertain significance ★★ same condition
NTRK2 p.Asn412Asp Uncertain significance ★★ ⚠ same condition
NTRK2 p.Cys19Tyr Uncertain significance ★★ ⚠ same condition
NTRK2 p.Gly480Ser 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/ntrk2-p-pro810 (accessed [today's date]).

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