Is NECAP1 p.Phe255= (c.765C>T) pathogenic?

NECAP1 p.Phe255= (c.765C>T) is classified Uncertain significance in NECAP1 (ClinVar, Single submitter, 1 submitter; last evaluated 2022-07-23). Absent from gnomAD v4.1; Associated with developmental and epileptic encephalopathy, 21.

What condition is associated with NECAP1 p.Phe255= (c.765C>T)?

NECAP1 p.Phe255= (c.765C>T) is associated with developmental and epileptic encephalopathy, 21 (ClinVar).

How common is NECAP1 p.Phe255= (c.765C>T) in the general population?

NECAP1 p.Phe255= (c.765C>T) is absent from gnomAD v4.1 (gnomAD).

NECAP1 p.Phe255=

Q: How is Non-specific early-onset epileptic encephalopathy inherited?

Typically Autosomal dominant, Autosomal recessive (Orphanet). A genetic counselor can assess individual risk for a family.

c.765C>T · rs750777115 · VCV2019217

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

gnomAD v4.1

Absent

absent from gnomAD v4.1

Conditions

developmental and epileptic encephalopathy, 21

Computational evidence

Protein change
Missense predictors do not apply to this variant type; conservation/SpliceAI carries the signal.
Splicing
SpliceAI	Δ0.39	donor gain · deltas
Pangolin	Δ0.34	gain · loss 0.22 · agrees with SpliceAI · independent
Constraint at this position
Conservation	phyloP -2.7	GERP -3.5
Overall
CADD	12.53	PHRED · no single calibrated threshold — expert panels disagree

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: NECAP1
Protein: p.Phe255=
Coding: c.765C>T
MANE Select: NM_015509
dbSNP: rs750777115
Type: single nucleotide variant
Location: chr12:8095689 (GRCh38)
Gene constraint: LOEUF 0.594 · pLI 0.68 (gnomAD)
Structure: AlphaFold pLDDT 70.78 · 2 PDB
Residue 255: the 'disordered' region

Full NECAP1 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Disease context

developmental and epileptic encephalopathy, 21 — disease report on Sugi Atlas → Associated genes, phenotypes, clinical trials & treatments

For Non-specific early-onset epileptic encephalopathy (Orphanet):

Inheritance: Autosomal dominant, Autosomal recessive, Not applicable
Onset: Infancy, Neonatal

Similar variants

NECAP1 p.Ala173Val Uncertain significance ★★ ⚠ same condition
NECAP1 p.Arg102His Uncertain significance ★★ ⚠ same condition
NECAP1 p.Arg146His Uncertain significance ★★ ⚠ same condition
NECAP1 p.Arg46Cys Uncertain significance ★★ ⚠ same condition
NECAP1 p.Asp118Asn Uncertain significance ★★ ⚠ same condition
NECAP1 p.Gly253Glu Uncertain significance ★★ ⚠ same condition
NECAP1 p.Gly45Ala Uncertain significance ★★ ⚠ same condition
NECAP1 p.His126Tyr 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/necap1-p-phe255 (accessed [today's date]).

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