NES p.Glu8=
c.24G>A · rs190174455 · VCV2639462
Likely benign
Single submitter
Classification
Likely benign
ClinVar
Review
Single submitter ★☆☆☆
ClinVar · 1 submitter
gnomAD v4.1
Rare
rare (popmax 0.414%, nfe)
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 0.31 | GERP -3.9, phastCons 1 |
| Overall | ||
| CADD | 9.96 | PHRED · no single calibrated threshold — expert panels disagree |
Population frequency
gnomAD v4.1 · exomes + genomes
Grpmax group
0.414%
European (non-Finnish) · 4,879/1,179,850 alleles
Filtering AF
0.404%
ClinGen BA1/BS1 input
FAF95, joint · FAF99 0.4%
Overall
0.356%
5,739/1,612,534 alleles · rare
exomes 5,314/1,460,192 · genomes 425/152,342 · joint denominator
| Ancestry group | Frequency | 1 in |
|---|---|---|
| European (non-Finnish)grpmax | 0.414% | 242 |
| Remaining individualsnot grpmax-eligible | 0.338% | 296 |
| South Asian | 0.328% | 305 |
| Admixed American | 0.283% | 353 |
| Finnishnot grpmax-eligible | 0.204% | 491 |
| African / African-American | 0.0667% | 1,500 |
| Middle Eastern | 0.0165% | 6,056 |
| Ashkenazi Jewishnot grpmax-eligible | 0.00338% | 29,598 |
| East Asian | 0.00223% | 44,834 |
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
- NES
- Protein
- p.Glu8=
- Coding
- c.24G>A
- MANE Select
- NM_006617
- dbSNP
- rs190174455
- Type
- single nucleotide variant
- Location
- chr1:156677241 (GRCh38)
- Gene constraint
- LOEUF 1.264 · pLI <0.01 (gnomAD)
- Structure
- AlphaFold pLDDT 49.18
- Residue 8
- the if rod domain; the 'coil 1a' region
Similar variants
- NES p.Glu8Val Uncertain significance ★★ ⚠ same residue
- NES p.Arg342Gln Benign ★★ same type
- NES p.Glu609Gln Benign ★★ same type
- NES p.Gly1407Arg Benign ★★ same type
- NES p.Leu412= Benign ★★ same type
- NES p.Lys830Arg Benign ★★ same type
- NES p.Pro1275Leu Benign ★★ same type
- NES p.Ser1466Gly 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/nes-p-glu8 (accessed [today's date]).
Preprint & method: sugi.bio/variant/method Machine-readable: this page as Markdown