Is NOS1 p.Ser300Phe (c.899C>T) pathogenic?

NOS1 p.Ser300Phe (c.899C>T) is classified Uncertain significance in NOS1 (ClinVar, Single submitter, 1 submitter; last evaluated 2023-06-29). AlphaMissense: ambiguous (0.3552); Very rare (popmax 0.00223%, eas).

How common is NOS1 p.Ser300Phe (c.899C>T) in the general population?

NOS1 p.Ser300Phe (c.899C>T) is very rare (popmax 0.00223%, eas) (gnomAD).

What do computational predictors say about NOS1 p.Ser300Phe (c.899C>T)?

AlphaMissense predicts ambiguous (score 0.3552) — an in-silico prediction, not a clinical call.

NOS1 p.Ser300Phe

c.899C>T · rs770763591 · VCV2608208

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

ambiguous

0.3552 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 0.00223%, eas)

Missense predictors

0/2 damaging

REVEL, SaProt · AlphaMissense indeterminate

Computational evidence

Protein change
AlphaMissense	0.3552	ambiguous
REVEL	0.238	benign-leaning
SaProt	LLR -8.81	tolerated
⇒ REVEL and SaProt both call this tolerated; AlphaMissense is indeterminate.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 12	GERP 2.3, phastCons 1
Overall
CADD	27.3	PHRED · no single calibrated threshold — expert panels disagree

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

Population frequency

gnomAD v4.1 · exomes + genomes

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

Overall 6.2e-05% 1/1,613,966 alleles · very rare exomes 1/1,461,690 · genomes 0/152,276 · joint denominator

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.Ser300Phe
Coding: c.899C>T
MANE Select: NM_000620
dbSNP: rs770763591
Type: single nucleotide variant
Location: chr12:117290380 (GRCh38)
Structure: AlphaFold pLDDT 61.90 · 1 PDB

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

Similar variants

NANOS1 c.-51G>C Benign ★★ same type
NANOS1 p.Pro34Thr Benign ★★ same type
NOS1 c.3042-6C>T Benign ★★ same type
NOS1 p.Ala1337= Likely benign ★★ same type
NOS1 p.Asp241Asn Benign/Likely benign ★★ same type
NOS1 p.Asp394Ala Benign/Likely benign ★★ same type
NOS1 p.Gly595Ser Benign/Likely benign ★★ same type
NOS1 p.Gly864Asp Likely 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/nos1-p-ser300phe (accessed [today's date]).

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