Is NOS2 p.Pro695Ser (c.2083C>T) pathogenic?

NOS2 p.Pro695Ser (c.2083C>T) is classified Uncertain significance in NOS2 (ClinVar, Single submitter, 1 submitter; last evaluated 2024-04-08). AlphaMissense: likely benign (0.2439); Absent from gnomAD v4.1.

How common is NOS2 p.Pro695Ser (c.2083C>T) in the general population?

NOS2 p.Pro695Ser (c.2083C>T) is absent from gnomAD v4.1 (gnomAD).

What do computational predictors say about NOS2 p.Pro695Ser (c.2083C>T)?

AlphaMissense predicts likely benign (score 0.2439) — an in-silico prediction, not a clinical call.

NOS2 p.Pro695Ser

c.2083C>T · VCV3300403

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.2439 · ACMG-weighted

gnomAD v4.1

Absent

absent from gnomAD v4.1

Missense predictors

1/3 damaging

AlphaMissense, REVEL, SaProt

Computational evidence

Protein change
AlphaMissense	0.2439	likely benign
REVEL	0.171	moderately benign-leaning
SaProt	LLR -10.01	damaging
⇒ SaProt calls this damaging; AlphaMissense and REVEL do not.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 12	GERP 1.7, phastCons 1
Overall
CADD	24.3	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

Absent from gnomAD v4.1. Not observed in any sequenced alleles — a rarity signal (ACMG PM2-supporting), not evidence of pathogenicity on its own.

Variant & gene context

Gene: NOS2
Protein: p.Pro695Ser
Coding: c.2083C>T
MANE Select: NM_000625
Type: single nucleotide variant
Location: chr17:27767789 (GRCh38)
Structure: AlphaFold pLDDT 76.58

Full NOS2 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Similar variants

NOS2 c.1005-10T>C Benign ★★ same type
NOS2 p.Arg1018Ser Likely benign ★★ same type
NOS2 p.Glu1111= Benign/Likely benign ★★ same type
NOS2 p.Gly360= Likely benign ★★ same type
NOS2 p.Phe319= Benign ★★ same type
NOS2 p.Val1110= Benign ★★ same type
NANOS2 p.Ala52Glu Uncertain significance ★ ⚠ same type
NANOS2 p.Ala52Val 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/nos2-p-pro695ser (accessed [today's date]).

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