Is NOS1 p.Pro867= (c.2601C>T) pathogenic?

NOS1 p.Pro867= (c.2601C>T) is classified Benign in NOS1 (ClinVar, No assertion criteria, 1 submitter; last evaluated 2019-02-16). Common (popmax 7.92%, afr) — too common for a highly-penetrant pathogenic allele; Associated with NOS1-related disorder.

What condition is associated with NOS1 p.Pro867= (c.2601C>T)?

NOS1 p.Pro867= (c.2601C>T) is associated with NOS1-related disorder (ClinVar).

NOS1 p.Pro867=

Q: How common is NOS1 p.Pro867= (c.2601C>T) in the general population?

NOS1 p.Pro867= (c.2601C>T) is common (popmax 7.92%, afr) — too common for a highly-penetrant pathogenic allele (gnomAD).

c.2601C>T · rs9658446 · VCV3055936

Benign No assertion criteria

Classification

Benign

ClinVar

Review

No assertion criteria ☆☆☆☆

ClinVar · 1 submitter

gnomAD v4.1

Common

common (popmax 7.92%, afr) — too common for a highly-penetrant pathogenic allele

Conditions

NOS1-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 -12	GERP -3.8
Overall
CADD	1.996	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 7.92% African / African-American · 5,941/74,966 alleles

Filtering AF 7.76% ClinGen BA1/BS1 input FAF95, joint · FAF99 7.69%

Overall 0.904% 14,583/1,613,904 alleles · common exomes 10,642/1,461,790 · genomes 3,941/152,114 · joint denominator

Ancestry group	Frequency	1 in
African / African-Americangrpmax	7.92%	13
South Asian	2.33%	43
Middle Eastern	2.05%	49
Remaining individualsnot grpmax-eligible	1.17%	85
Admixed American	1.13%	88
Ashkenazi Jewishnot grpmax-eligible	1.04%	96
European (non-Finnish)	0.395%	253
Finnishnot grpmax-eligible	0.0344%	2,910
East Asian	0.0134%	7,478

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: NOS1
Protein: p.Pro867=
Coding: c.2601C>T
MANE Select: NM_000620
dbSNP: rs9658446
Type: single nucleotide variant
Location: chr12:117253685 (GRCh38)
Structure: AlphaFold pLDDT 61.90 · 1 PDB

Full NOS1 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Disease context

NOS1-related disorder

Similar variants

NOS1 p.Met619Leu Conflicting classifications of pathogenicity ★ ⚠ same condition
NOS1 c.2532-2233A>G Benign same condition
NOS1 c.2532-2256C>A Benign same condition
NOS1 c.2532-2258C>T Benign same condition
NOS1 c.*8C>T Benign same condition
NOS1 p.Asn1075= Likely benign same condition
NOS1 p.Asn532= Likely benign same condition
NOS1 p.Asp1086= Benign 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/nos1-p-pro867 (accessed [today's date]).

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