Is NTRK2 p.Arg792Cys (c.2374C>T) pathogenic?

NTRK2 p.Arg792Cys (c.2374C>T) is classified Conflicting classifications of pathogenicity in NTRK2 (ClinVar, Conflicting submitters, 4 submitters; last evaluated 2025-11-12). AlphaMissense: likely pathogenic (0.8493); Very rare (popmax 0.00223%, eas); Associated with Developmental disorder.

What condition is associated with NTRK2 p.Arg792Cys (c.2374C>T)?

NTRK2 p.Arg792Cys (c.2374C>T) is associated with Developmental disorder (ClinVar).

How common is NTRK2 p.Arg792Cys (c.2374C>T) in the general population?

NTRK2 p.Arg792Cys (c.2374C>T) is very rare (popmax 0.00223%, eas) (gnomAD).

What do computational predictors say about NTRK2 p.Arg792Cys (c.2374C>T)?

AlphaMissense predicts likely pathogenic (score 0.8493) — an in-silico prediction, not a clinical call.

NTRK2 p.Arg792Cys

c.2374C>T · rs201902834 · VCV1343169

Conflicting classifications of pathogenicity Conflicting submitters

Classification

Conflicting classifications of pathogenicity

ClinVar

Review

Conflicting submitters ★☆☆☆

ClinVar · 4 submitters

AlphaMissense

likely pathogenic

0.8493 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 0.00223%, eas)

Missense predictors

2/3 damaging

AlphaMissense, REVEL, SaProt

Conditions

Developmental disorder

Computational evidence

Protein change
AlphaMissense	0.8493	likely pathogenic
REVEL	0.716	pathogenic-leaning
SaProt	LLR -2.45	tolerated
⇒ AlphaMissense and REVEL call this damaging; SaProt does not.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 4.3	GERP 1.9, phastCons 1
Regional constraint	o/e 0.38	unconstrained · MANE · 66 kb · p 7.2e-19 · regional, not allelic
Overall
CADD	32.0	PHRED · no single calibrated threshold — expert panels disagree

AlphaMissense carries the ACMG weight for missense; REVEL and SaProt are independent agreement signals.

⚠ Isoform check: AlphaMissense numbered on a different transcript (AM R776C vs ClinVar R792C) — verify the residue.

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.00223% East Asian · 1/44,874 alleles

Filtering AF 0.00138% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.00116%

Overall 0.00161% 26/1,613,974 alleles · very rare exomes 20/1,461,854 · genomes 6/152,120 · joint denominator

Ancestry group	Frequency	1 in
East Asiangrpmax	0.00223%	44,874
European (non-Finnish)	0.00203%	49,168
South Asian	0.0011%	91,076

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.Arg792Cys
Coding: c.2374C>T
MANE Select: NM_006180
dbSNP: rs201902834
Type: single nucleotide variant
Location: chr9:85021294 (GRCh38)
Gene constraint: LOEUF 0.123 · pLI 1.00 (gnomAD)
Structure: AlphaFold pLDDT 77.53 · 9 PDB
Residue 776 UniProt numbering: the protein kinase domain; a UniProt-annotated variant site (in obhd)

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

Disease context

Developmental disorder — disease report on Sugi Atlas → Associated genes, phenotypes, clinical trials & treatments

Similar variants

NTRK2 p.Arg792His Uncertain significance ★ ⚠ same residue
NTRK2 p.Arg124Ter Conflicting classifications of pathogenicity ★ ⚠ same condition
NTRK2 p.Arg792fs Uncertain significance ★ same residue
NTRK2 p.Cys805Arg Uncertain significance ★ ⚠ same condition
NTRK2 p.Arg551Gln Likely pathogenic ★★ same type
NTRK2 p.Tyr434Cys Pathogenic/Likely pathogenic ★★ ⚠ same type
NTRK2 p.Ala440Val Uncertain significance ★★ ⚠ same type
NTRK2 p.Arg124Gly Uncertain significance ★★ ⚠ same type

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-arg792cys (accessed [today's date]).

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