Is NECAP1 p.Pro198= (c.594C>T) pathogenic?

NECAP1 p.Pro198= (c.594C>T) is classified Likely benign in NECAP1 (ClinVar, Single submitter, 1 submitter; last evaluated 2019-07-05). Very rare (popmax 8.48e-05%, nfe); Associated with developmental and epileptic encephalopathy, 21.

What condition is associated with NECAP1 p.Pro198= (c.594C>T)?

NECAP1 p.Pro198= (c.594C>T) is associated with developmental and epileptic encephalopathy, 21 (ClinVar).

How common is NECAP1 p.Pro198= (c.594C>T) in the general population?

NECAP1 p.Pro198= (c.594C>T) is very rare (popmax 8.48e-05%, nfe) (gnomAD).

NECAP1 p.Pro198=

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.594C>T · rs1947563520 · VCV1158541

Likely benign Single submitter

Classification

Likely benign

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

gnomAD v4.1

Rare

very rare (popmax 8.48e-05%, nfe)

Conditions

developmental and epileptic encephalopathy, 21

Computational evidence

Protein change
Missense predictors do not apply to this variant type; conservation carries the signal.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP -2.4	GERP -1.1
Overall
CADD	8.617	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 8.48e-05% European (non-Finnish) · 1/1,179,146 alleles

Overall 6.2e-05% 1/1,612,200 alleles · very rare exomes 1/1,459,900 · genomes 0/152,300 · 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: NECAP1
Protein: p.Pro198=
Coding: c.594C>T
MANE Select: NM_015509
dbSNP: rs1947563520
Type: single nucleotide variant
Location: chr12:8092973 (GRCh38)
Gene constraint: LOEUF 0.594 · pLI 0.68 (gnomAD)
Structure: AlphaFold pLDDT 70.78 · 2 PDB

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-pro198 (accessed [today's date]).

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