Is NOS1 p.Phe262Val (c.784T>G) pathogenic?

NOS1 p.Phe262Val (c.784T>G) is classified Likely benign in NOS1 (ClinVar, Single submitter, 1 submitter; last evaluated 2024-03-01). AlphaMissense: likely benign (0.1608); Ultra-rare (popmax 0.0519%, nfe).

How common is NOS1 p.Phe262Val (c.784T>G) in the general population?

NOS1 p.Phe262Val (c.784T>G) is ultra-rare (popmax 0.0519%, nfe) (gnomAD).

What do computational predictors say about NOS1 p.Phe262Val (c.784T>G)?

AlphaMissense predicts likely benign (score 0.1608) — an in-silico prediction, not a clinical call.

NOS1 p.Phe262Val

c.784T>G · rs200602438 · VCV2570851

Likely benign Single submitter

Classification

Likely benign

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.1608 · ACMG-weighted

gnomAD v4.1

Rare

ultra-rare (popmax 0.0519%, nfe)

Missense predictors

0/3 damaging

AlphaMissense, REVEL, SaProt

Computational evidence

Protein change
AlphaMissense	0.1608	likely benign
REVEL	0.077	moderately benign-leaning
SaProt	LLR -5.23	tolerated
⇒ AlphaMissense, REVEL and SaProt all call this tolerated.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 1	GERP -1.1, phastCons 0.99
Overall
CADD	17.18	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 0.0519% European (non-Finnish) · 612/1,179,608 alleles

Filtering AF 0.0484% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.0471%

Overall 0.045% 726/1,613,154 alleles · ultra-rare exomes 694/1,460,820 · genomes 32/152,334 · joint denominator

Ancestry group	Frequency	1 in
Ashkenazi Jewishnot grpmax-eligible	0.267%	375
European (non-Finnish)grpmax	0.0519%	1,927
Remaining individualsnot grpmax-eligible	0.04%	2,499
Admixed American	0.00835%	11,978
African / African-American	0.00666%	15,010

Ashkenazi Jewish 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: NOS1
Protein: p.Phe262Val
Coding: c.784T>G
MANE Select: NM_000620
dbSNP: rs200602438
Type: single nucleotide variant
Location: chr12:117311534 (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-phe262val (accessed [today's date]).

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