Is NTSR2 p.Arg287Cys (c.859C>T) pathogenic?

NTSR2 p.Arg287Cys (c.859C>T) is classified Uncertain significance in NTSR2 (ClinVar, Single submitter, 1 submitter; last evaluated 2024-08-01). AlphaMissense: likely benign (0.0896); Rare (popmax 0.204%, sas).

How common is NTSR2 p.Arg287Cys (c.859C>T) in the general population?

NTSR2 p.Arg287Cys (c.859C>T) is rare (popmax 0.204%, sas) (gnomAD).

What do computational predictors say about NTSR2 p.Arg287Cys (c.859C>T)?

AlphaMissense predicts likely benign (score 0.0896) — an in-silico prediction, not a clinical call.

NTSR2 p.Arg287Cys

c.859C>T · VCV3408320

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.0896 · ACMG-weighted

gnomAD v4.1

Rare

rare (popmax 0.204%, sas)

Missense predictors

0/3 damaging

AlphaMissense, REVEL, SaProt

Computational evidence

Protein change
AlphaMissense	0.0896	likely benign
REVEL	0.228	benign-leaning
SaProt	LLR -9.61	tolerated
⇒ AlphaMissense, REVEL and SaProt all call this tolerated.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP -0.36	GERP -2.7, phastCons 0.25
Regional constraint	o/e 1.00	unconstrained · MANE · 12 kb · p 0.99 · regional, not allelic
Overall
CADD	12.66	PHRED · no single calibrated threshold — expert panels disagree

ClinVar classifies this uncertain; the computational predictors unanimously lean tolerated — a triage signal, not a reclassification

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

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.204% South Asian · 185/90,680 alleles

Filtering AF 0.18% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.171%

Overall 0.0132% 213/1,611,222 alleles · rare exomes 198/1,458,922 · genomes 15/152,300 · joint denominator

Ancestry group	Frequency	1 in
South Asiangrpmax	0.204%	490
Remaining individualsnot grpmax-eligible	0.0128%	7,795
East Asian	0.00894%	11,182
African / African-American	0.008%	12,493
Admixed American	0.00503%	19,895
European (non-Finnish)	0.000594%	168,377

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: NTSR2
Protein: p.Arg287Cys
Coding: c.859C>T
MANE Select: NM_012344
Type: single nucleotide variant
Location: chr2:11662006 (GRCh38)
Gene constraint: LOEUF 1.731 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 79.25

Full NTSR2 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Similar variants

NTSR2 p.Arg287His Uncertain significance ★ ⚠ same residue
NTSR2 p.Arg282Lys Benign ★★ same type
NTSR2 p.Ala190Thr Uncertain significance ★ ⚠ same type
NTSR2 p.Ala327Val Uncertain significance ★ ⚠ same type
NTSR2 p.Ala360Thr Uncertain significance ★ ⚠ same type
NTSR2 p.Ala47Val Uncertain significance ★ ⚠ same type
NTSR2 p.Ala62Thr Uncertain significance ★ ⚠ same type
NTSR2 p.Ala65Thr 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/ntsr2-p-arg287cys (accessed [today's date]).

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