Is NCKAP1 p.Phe296fs (c.885_886del) pathogenic?

NCKAP1 p.Phe296fs (c.885886del) is classified Likely pathogenic in NCKAP1 (ClinVar, Single submitter, 1 submitter; last evaluated 2024-11-09). Absent from gnomAD v4.1; Associated with NCKAP1-related neurodevelopmental disorder with autism features.

What condition is associated with NCKAP1 p.Phe296fs (c.885_886del)?

NCKAP1 p.Phe296fs (c.885_886del) is associated with NCKAP1-related neurodevelopmental disorder with autism features (ClinVar).

How common is NCKAP1 p.Phe296fs (c.885_886del) in the general population?

NCKAP1 p.Phe296fs (c.885_886del) is absent from gnomAD v4.1 (gnomAD).

NCKAP1 p.Phe296fs

c.885_886del · VCV4293564

Likely pathogenic Single submitter

Classification

Likely pathogenic

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

Consequence

frameshift

predicted LoF

gnomAD v4.1

Not reported

no allele count reported in gnomAD v4.1 (AN 1,613,900)

Conditions

NCKAP1-related neurodevelopmental disorder with autism features

Computational evidence

Protein change
Missense predictors do not apply to this variant type; conservation carries the signal.
Consequence	frameshift	predicted loss-of-function in a haploinsufficient gene (ClinGen)
NMD	predicted	premature termination codon in exon 9 of 31
Splicing
SpliceAI	—	not assessed · substitutions only
Constraint at this position
Conservation	phyloP 11	GERP 2.1, phastCons 1

Predicted loss-of-function is descriptive, not an applied PVS1 code.

Population frequency

gnomAD v4.1 · exomes + genomes

No allele count reported in gnomAD v4.1 (AN 1,613,900). This is missing data, not an absence: the variant may or may not be present in gnomAD. Rarity (ACMG PM2) and BA1/BS1 cannot be assessed for it.

Variant & gene context

Gene: NCKAP1
Protein: p.Phe296fs
Coding: c.885_886del
MANE Select: NM_013436
Type: Microsatellite
Location: chr2:182989091 (GRCh38)
Gene constraint: LOEUF 0.14 · pLI 1.00 · ClinGen HI 3/3 (gnomAD)
Structure: AlphaFold pLDDT 92.75 · 5 PDB
Residue 296: a β-strand

Full NCKAP1 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Disease context

NCKAP1-related neurodevelopmental disorder with autism features

Similar variants

NCKAP1 c.3180+2del Likely pathogenic ★ same condition
NCKAP1 p.Gln228fs Likely pathogenic ★ same condition
NCKAP1 p.Lys501fs Likely pathogenic ★ same condition
NCKAP1 p.Pro704fs Pathogenic ★ same condition
NCKAP1 p.Ser710fs Likely pathogenic ★ same condition
NCKAP1 p.Arg715Ser Uncertain significance ★ ⚠ same condition
NCKAP1 p.Asp122Asn Uncertain significance ★ ⚠ same condition
NCKAP1 p.Asp128fs 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/nckap1-p-phe296fs (accessed [today's date]).

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