Is NEBL p.Pro799Ser (c.2395C>T) pathogenic?

NEBL p.Pro799Ser (c.2395C>T) is classified Conflicting classifications of pathogenicity in NEBL (ClinVar, Conflicting submitters, 2 submitters; last evaluated 2024-11-18). AlphaMissense: likely benign (0.266); Ultra-rare (popmax 0.0736%, eas); Associated with dilated cardiomyopathy.

What condition is associated with NEBL p.Pro799Ser (c.2395C>T)?

NEBL p.Pro799Ser (c.2395C>T) is associated with dilated cardiomyopathy (ClinVar).

How common is NEBL p.Pro799Ser (c.2395C>T) in the general population?

NEBL p.Pro799Ser (c.2395C>T) is ultra-rare (popmax 0.0736%, eas) (gnomAD).

What do computational predictors say about NEBL p.Pro799Ser (c.2395C>T)?

AlphaMissense predicts likely benign (score 0.266) — an in-silico prediction, not a clinical call.

NEBL p.Pro799Ser

c.2395C>T · rs566320226 · VCV697036

Conflicting classifications of pathogenicity Conflicting submitters

Classification

Conflicting classifications of pathogenicity

ClinVar

Review

Conflicting submitters ★☆☆☆

ClinVar · 2 submitters

AlphaMissense

likely benign

0.266 · ACMG-weighted

gnomAD v4.1

Rare

ultra-rare (popmax 0.0736%, eas)

Missense predictors

0/3 damaging

AlphaMissense, REVEL, SaProt

Conditions

dilated cardiomyopathy

Computational evidence

Protein change
AlphaMissense	0.266	likely benign
REVEL	0.239	benign-leaning
SaProt	LLR -5.50	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 12	GERP 2.4, phastCons 1
Regional constraint	o/e 1.15	unconstrained · MANE · 111 kb · p 7.4e-07 · regional, not allelic
Overall
CADD	23.6	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 0.0736% East Asian · 33/44,850 alleles

Filtering AF 0.0538% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.0471%

Overall 0.00229% 37/1,613,990 alleles · ultra-rare exomes 32/1,461,722 · genomes 5/152,268 · joint denominator

Ancestry group	Frequency	1 in
East Asiangrpmax	0.0736%	1,359
Remaining individualsnot grpmax-eligible	0.0032%	31,253
South Asian	0.0011%	91,084
European (non-Finnish)	8.48e-05%	1,179,920

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.Pro799Ser
Coding: c.2395C>T
MANE Select: NM_006393
dbSNP: rs566320226
Type: single nucleotide variant
Location: chr10:20812892 (GRCh38)
Gene constraint: LOEUF 1.036 · pLI <0.01 · ClinGen HI 0/3 (gnomAD)
Structure: AlphaFold pLDDT 62.00 · 1 PDB

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

Disease context

dilated cardiomyopathy — disease report on Sugi Atlas → Associated genes, phenotypes, clinical trials & treatments

Similar variants

NEBL p.Pro799= Likely benign ★★ same residue
NEBL p.Pro799Ala Uncertain significance ★ ⚠ same residue
NEBL c.1227+5G>A Uncertain significance ★★ same condition
NEBL c.1870-1G>A Uncertain significance ★★ same condition
NEBL c.798+1G>A Uncertain significance ★★ same condition
NEBL c.903+1G>T Uncertain significance ★★ same condition
NEBL p.Ala114Ser Uncertain significance ★★ ⚠ same condition
NEBL p.Ala219Thr Uncertain significance ★★ ⚠ same condition

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-pro799ser (accessed [today's date]).

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