Is NOS1AP p.Arg235= (c.705A>G) pathogenic?

NOS1AP p.Arg235= (c.705A>G) is classified Likely benign in NOS1AP (ClinVar, Single submitter, 1 submitter; last evaluated 2018-10-31). Very rare (popmax 0.00667%, amr).

How common is NOS1AP p.Arg235= (c.705A>G) in the general population?

NOS1AP p.Arg235= (c.705A>G) is very rare (popmax 0.00667%, amr) (gnomAD).

NOS1AP p.Arg235=

c.705A>G · VCV4919988

Likely benign Single submitter

Classification

Likely benign

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

gnomAD v4.1

Rare

very rare (popmax 0.00667%, amr)

Computational evidence

Protein change
Missense predictors do not apply to this variant type; conservation carries the signal.
Splicing
SpliceAI	<0.2	no splice effect predicted · four deltas, not one · how we know
Constraint at this position
Conservation	phyloP -1.3	GERP -5
Overall
CADD	4.491	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.00667% Admixed American · 4/60,008 alleles

Filtering AF 0.00226% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.00135%

Overall 0.00167% 27/1,614,086 alleles · very rare exomes 27/1,461,894 · genomes 0/152,192 · joint denominator

Ancestry group	Frequency	1 in
Admixed Americangrpmax	0.00667%	15,002
African / African-American	0.00267%	37,503
European (non-Finnish)	0.00169%	59,001
Remaining individualsnot grpmax-eligible	0.0016%	62,506

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: NOS1AP
Protein: p.Arg235=
Coding: c.705A>G
MANE Select: NM_014697
Type: single nucleotide variant
Location: chr1:162355296 (GRCh38)
Gene constraint: LOEUF 0.495 · pLI 0.98 (gnomAD)
Structure: AlphaFold pLDDT 65.59

Full NOS1AP gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Similar variants

NOS1AP p.Lys427Arg Uncertain significance ★★ ⚠ same type
NOS1AP p.Pro402Leu Uncertain significance ★★ ⚠ same type
NOS1AP c.1105+65T>C Benign ★★ same type
NOS1AP c.178-101C>G Benign ★★ same type
NOS1AP c.270+55A>G Benign ★★ same type
NOS1AP c.345-118C>T Benign ★★ same type
NOS1AP c.345-172T>C Benign ★★ same type
NOS1AP c.454-107A>G 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/nos1ap-p-arg235 (accessed [today's date]).

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