Is NOS2 p.Asp385= (c.1155C>T) pathogenic?

NOS2 p.Asp385= (c.1155C>T) is classified Benign in NOS2 (ClinVar, Single submitter, 2 submitters; last evaluated 2024-01-24). Common (popmax 23.6%, mid) — too common for a highly-penetrant pathogenic allele.

NOS2 p.Asp385=

Q: How common is NOS2 p.Asp385= (c.1155C>T) in the general population?

NOS2 p.Asp385= (c.1155C>T) is common (popmax 23.6%, mid) — too common for a highly-penetrant pathogenic allele (gnomAD).

c.1155C>T · rs1137933 · VCV2688251

Benign Single submitter

Classification

Benign

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 2 submitters

gnomAD v4.1

Common

common (popmax 23.6%, mid) — too common for a highly-penetrant pathogenic allele

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 -3.9	GERP -3.7
Overall
CADD	2.92	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 23.6% Middle Eastern · 1,423/6,032 alleles

Filtering AF 22.6% ClinGen BA1/BS1 input FAF95, joint · FAF99 22.3%

Overall 21.5% 345,549/1,606,554 alleles · common exomes 314,117/1,454,584 · genomes 31,432/151,970 · joint denominator

Ancestry group	Frequency	1 in
Amishnot grpmax-eligible	44.4%	2
Ashkenazi Jewishnot grpmax-eligible	27.2%	4
Middle Easterngrpmax	23.6%	4
European (non-Finnish)	22.4%	4
Remaining individualsnot grpmax-eligible	21.3%	5
Finnishnot grpmax-eligible	21%	5
South Asian	19.2%	5
African / African-American	17.9%	6
Admixed American	15.7%	6
East Asian	12.3%	8

Amish shows a higher raw frequency than the grpmax group above it. gnomAD excludes bottlenecked groups — Finnish, Ashkenazi Jewish, Amish and “Remaining individuals” — from grpmax, because founder effects make their frequencies unrepresentative for filtering. The table is sorted by frequency, so an excluded group can sit above the grpmax row.

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: NOS2
Protein: p.Asp385=
Coding: c.1155C>T
MANE Select: NM_000625
dbSNP: rs1137933
Type: single nucleotide variant
Location: chr17:27778906 (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-asp385 (accessed [today's date]).

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