Is NEBL p.Phe797Ser (c.2390T>C) pathogenic?

NEBL p.Phe797Ser (c.2390T>C) is classified Uncertain significance in NEBL (ClinVar, Single submitter, 1 submitter; last evaluated 2024-04-30). AlphaMissense: likely pathogenic (0.9447); Absent from gnomAD v4.1; Associated with dilated cardiomyopathy.

What condition is associated with NEBL p.Phe797Ser (c.2390T>C)?

NEBL p.Phe797Ser (c.2390T>C) is associated with dilated cardiomyopathy (ClinVar).

How common is NEBL p.Phe797Ser (c.2390T>C) in the general population?

NEBL p.Phe797Ser (c.2390T>C) is absent from gnomAD v4.1 (gnomAD).

What do computational predictors say about NEBL p.Phe797Ser (c.2390T>C)?

AlphaMissense predicts likely pathogenic (score 0.9447) — an in-silico prediction, not a clinical call.

NEBL p.Phe797Ser

c.2390T>C · rs1838312385 · VCV1001083

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely pathogenic

0.9447 · ACMG-weighted

gnomAD v4.1

Absent

absent from gnomAD v4.1

Missense predictors

1/2 damaging

AlphaMissense, SaProt · REVEL no call

Conditions

dilated cardiomyopathy

Computational evidence

Protein change
AlphaMissense	0.9447	likely pathogenic · top 3% in NEBL
REVEL	0.347	indeterminate
SaProt	LLR -7.28	tolerated
⇒ AlphaMissense calls this damaging; SaProt does not; REVEL makes no call.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 11	GERP 2.4, phastCons 1
Regional constraint	o/e 1.15	unconstrained · MANE · 111 kb · p 7.4e-07 · regional, not allelic
Overall
CADD	24.1	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

Absent from gnomAD v4.1. Not observed in any sequenced alleles — a rarity signal (ACMG PM2-supporting), not evidence of pathogenicity on its own.

Variant & gene context

Gene: NEBL
Protein: p.Phe797Ser
Coding: c.2390T>C
MANE Select: NM_006393
dbSNP: rs1838312385
Type: single nucleotide variant
Location: chr10:20812897 (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.Phe797Leu 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
NEBL p.Ala264Val 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-phe797ser (accessed [today's date]).

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