Is NOS1 p.Phe887= (c.2661T>C) pathogenic?

NOS1 p.Phe887= (c.2661T>C) is classified Likely benign in NOS1 (ClinVar, No assertion criteria, 1 submitter; last evaluated 2019-08-16). Very rare (popmax 0.00779%, sas); Associated with NOS1-related disorder.

What condition is associated with NOS1 p.Phe887= (c.2661T>C)?

NOS1 p.Phe887= (c.2661T>C) is associated with NOS1-related disorder (ClinVar).

How common is NOS1 p.Phe887= (c.2661T>C) in the general population?

NOS1 p.Phe887= (c.2661T>C) is very rare (popmax 0.00779%, sas) (gnomAD).

NOS1 p.Phe887=

c.2661T>C · rs752133783 · VCV3052307

Likely benign No assertion criteria

Classification

Likely benign

ClinVar

Review

No assertion criteria ☆☆☆☆

ClinVar · 1 submitter

gnomAD v4.1

Rare

very rare (popmax 0.00779%, sas)

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 -4	GERP -4.9
Overall
CADD	0.102	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.00779% South Asian · 7/89,868 alleles

Filtering AF 0.00363% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.00258%

Overall 0.00193% 31/1,606,534 alleles · very rare exomes 25/1,454,588 · genomes 6/151,946 · joint denominator

Ancestry group	Frequency	1 in
South Asiangrpmax	0.00779%	12,838
European (non-Finnish)	0.00195%	51,166
Remaining individualsnot grpmax-eligible	0.00161%	62,222

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.Phe887=
Coding: c.2661T>C
MANE Select: NM_000620
dbSNP: rs752133783
Type: single nucleotide variant
Location: chr12:117247510 (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-phe887 (accessed [today's date]).

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