Is NTSR1 p.Pro11Arg (c.32C>G) pathogenic?

NTSR1 p.Pro11Arg (c.32C>G) is classified Uncertain significance in NTSR1 (ClinVar, Single submitter, 1 submitter; last evaluated 2023-07-19). AlphaMissense: likely benign (0.0557); Very rare (popmax 0.00251%, eas).

How common is NTSR1 p.Pro11Arg (c.32C>G) in the general population?

NTSR1 p.Pro11Arg (c.32C>G) is very rare (popmax 0.00251%, eas) (gnomAD).

What do computational predictors say about NTSR1 p.Pro11Arg (c.32C>G)?

AlphaMissense predicts likely benign (score 0.0557) — an in-silico prediction, not a clinical call.

NTSR1 p.Pro11Arg

c.32C>G · rs1470757486 · VCV2612973

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.0557 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 0.00251%, eas)

Missense predictors

0/3 damaging

AlphaMissense, REVEL, SaProt

Computational evidence

Protein change
AlphaMissense	0.0557	likely benign
REVEL	0.042	moderately benign-leaning
SaProt	LLR -9.07	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 -0.87	GERP -2.3
Regional constraint	o/e 1.17	unconstrained · MANE · 51 kb · p 3.1e-05 · regional, not allelic
Overall
CADD	0.378	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 0.00251% East Asian · 1/39,910 alleles

Overall 0.000133% 2/1,502,536 alleles · very rare exomes 1/1,350,318 · genomes 1/152,218 · joint denominator

Ancestry group	Frequency	1 in
East Asiangrpmax	0.00251%	39,910
European (non-Finnish)	8.82e-05%	1,133,189

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: NTSR1
Protein: p.Pro11Arg
Coding: c.32C>G
MANE Select: NM_002531
dbSNP: rs1470757486
Type: single nucleotide variant
Location: chr20:62709239 (GRCh38)
Gene constraint: LOEUF 1.261 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 80.27 · 48 PDB

Full NTSR1 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Similar variants

NTSR1 p.Pro11Ser Uncertain significance ★ ⚠ same residue
NTSR1 p.Pro11Thr Uncertain significance ★ ⚠ same residue
NTSR1 c.917-6C>A Benign ★★ same type
NTSR1 p.Arg388Cys Benign ★★ same type
NTSR1 p.Arg45= Benign ★★ same type
NTSR1 p.Gln275His Benign ★★ same type
NTSR1 p.Gly301= Benign ★★ same type
NTSR1 p.Ser39= Benign ★★ 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/ntsr1-p-pro11arg (accessed [today's date]).

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