Is NEBL p.Arg845= (c.2535C>T) pathogenic?

NEBL p.Arg845= (c.2535C>T) is classified Likely benign in NEBL (ClinVar, Single submitter, 1 submitter; last evaluated 2024-04-26). Very rare (popmax 0.00135%, afr).

How common is NEBL p.Arg845= (c.2535C>T) in the general population?

NEBL p.Arg845= (c.2535C>T) is very rare (popmax 0.00135%, afr) (gnomAD).

NEBL p.Arg845=

c.2535C>T · VCV3299115

Likely benign Single submitter

Classification

Likely benign

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

gnomAD v4.1

Rare

very rare (popmax 0.00135%, afr)

Computational evidence

Protein change
Missense predictors do not apply to this variant type; conservation carries the signal.
Splicing
SpliceAI	<0.2	all four deltas below 0.2 · G>C here scores Δ0.20 · evaluated, not missing
Constraint at this position
Conservation	phyloP 1.3	GERP -1.9, phastCons 1
Overall
CADD	11.51	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.00135% African / African-American · 1/74,294 alleles

Overall 6.2e-05% 1/1,611,614 alleles · very rare exomes 0/1,461,168 · genomes 1/150,446 · joint denominator

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: NEBL
Protein: p.Arg845=
Coding: c.2535C>T
MANE Select: NM_006393
Type: single nucleotide variant
Location: chr10:20809882 (GRCh38)
Gene constraint: LOEUF 1.036 · pLI <0.01 · ClinGen HI 0/3 (gnomAD)
Structure: AlphaFold pLDDT 62.00 · 1 PDB
Residue 845: the 'linker' region

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

Similar variants

NEBL p.Arg845Cys Uncertain significance ★ ⚠ same residue
NEBL p.Arg845His Conflicting classifications of pathogenicity ★ same residue
NEBL p.Arg845Pro Uncertain significance ★ ⚠ same residue
NEBL c.1227+5G>A Uncertain significance ★★ same type
NEBL c.1870-1G>A Uncertain significance ★★ same type
NEBL c.798+1G>A Uncertain significance ★★ same type
NEBL c.903+1G>T Uncertain significance ★★ same type
NEBL p.Ala114Ser 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/nebl-p-arg845 (accessed [today's date]).

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