Is NEBL p.Phe852= (c.2556C>T) pathogenic?

NEBL p.Phe852= (c.2556C>T) is classified Likely benign in NEBL (ClinVar, No assertion criteria, 1 submitter; last evaluated 2019-03-13). Very rare (popmax 0.00448%, eas); Associated with NEBL-related disorder.

What condition is associated with NEBL p.Phe852= (c.2556C>T)?

NEBL p.Phe852= (c.2556C>T) is associated with NEBL-related disorder (ClinVar).

How common is NEBL p.Phe852= (c.2556C>T) in the general population?

NEBL p.Phe852= (c.2556C>T) is very rare (popmax 0.00448%, eas) (gnomAD).

NEBL p.Phe852=

c.2556C>T · rs774968429 · VCV3046591

Likely benign No assertion criteria

Classification

Likely benign

ClinVar

Review

No assertion criteria ☆☆☆☆

ClinVar · 1 submitter

gnomAD v4.1

Rare

very rare (popmax 0.00448%, eas)

Conditions

NEBL-related disorder

Computational evidence

Protein change
Missense predictors do not apply to this variant type; conservation/SpliceAI carries the signal.
Splicing
SpliceAI	Δ0.26	acceptor loss · deltas
Pangolin	Δ0.27	loss · gain 0.00 · agrees with SpliceAI · independent
Constraint at this position
Conservation	phyloP 4.6	GERP -0.9, phastCons 1
Overall
CADD	14.08	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.00448% East Asian · 2/44,612 alleles

Filtering AF 0.000743% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.000278%

Overall 0.00112% 18/1,610,826 alleles · very rare exomes 17/1,460,770 · genomes 1/150,056 · joint denominator

Ancestry group	Frequency	1 in
Finnishnot grpmax-eligible	0.00947%	10,562
East Asiangrpmax	0.00448%	22,306
Remaining individualsnot grpmax-eligible	0.0016%	62,398
African / African-American	0.00135%	74,232
South Asian	0.0011%	90,944
European (non-Finnish)	0.000594%	168,440

Finnish 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: NEBL
Protein: p.Phe852=
Coding: c.2556C>T
MANE Select: NM_006393
dbSNP: rs774968429
Type: single nucleotide variant
Location: chr10:20809861 (GRCh38)
Gene constraint: LOEUF 1.036 · pLI <0.01 · ClinGen HI 0/3 (gnomAD)
Structure: AlphaFold pLDDT 62.00 · 1 PDB
Residue 852: the 'linker' region

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

Disease context

NEBL-related disorder

Similar variants

NEBL p.Ser482Arg Uncertain significance ★ ⚠ same condition
NEBL p.Tyr959Cys Uncertain significance ★ ⚠ same condition
NEBL p.Gly724Glu Uncertain significance ⚠ same condition
NEBL p.Phe98= Likely benign same condition
NEBL p.Asp390_Leu391insTer Uncertain significance same condition
NEBL c.259-9_259-8dup Likely benign same condition
NEBL c.1227+5G>A Uncertain significance ★★ same type
NEBL c.1870-1G>A 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-phe852 (accessed [today's date]).

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