Is NCKAP1 p.Arg669Ser (c.2007G>T) pathogenic?

NCKAP1 p.Arg669Ser (c.2007G>T) is classified Likely pathogenic in NCKAP1 (ClinVar, Single submitter, 1 submitter; last evaluated 2024-09-20). AlphaMissense: likely pathogenic (0.9963); Absent from gnomAD v4.1; Associated with neurodevelopmental disorder.

What condition is associated with NCKAP1 p.Arg669Ser (c.2007G>T)?

NCKAP1 p.Arg669Ser (c.2007G>T) is associated with neurodevelopmental disorder (ClinVar).

How common is NCKAP1 p.Arg669Ser (c.2007G>T) in the general population?

NCKAP1 p.Arg669Ser (c.2007G>T) is absent from gnomAD v4.1 (gnomAD).

What do computational predictors say about NCKAP1 p.Arg669Ser (c.2007G>T)?

AlphaMissense predicts likely pathogenic (score 0.9963) — an in-silico prediction, not a clinical call.

NCKAP1 p.Arg669Ser

c.2007G>T · VCV3376855

Likely pathogenic Single submitter

Classification

Likely pathogenic

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely pathogenic

0.9963 · ACMG-weighted

gnomAD v4.1

Absent

absent from gnomAD v4.1

Missense predictors

1/2 damaging

AlphaMissense, SaProt · REVEL indeterminate

Conditions

neurodevelopmental disorder

Computational evidence

Protein change
AlphaMissense	0.9963	likely pathogenic ✓ concordant with ClinVar · top 10% in NCKAP1
REVEL	0.455	indeterminate
SaProt	LLR -5.76	tolerated
⇒ AlphaMissense calls this damaging; SaProt does not; REVEL is indeterminate.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP -0.66	GERP -3, phastCons 0.011
Regional constraint	o/e 0.59	unconstrained · MANE · 32 kb · p 1.2e-22 · regional, not allelic
Overall
CADD	22.6	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

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: NCKAP1
Protein: p.Arg669Ser
Coding: c.2007G>T
MANE Select: NM_013436
Type: single nucleotide variant
Location: chr2:182957471 (GRCh38)
Gene constraint: LOEUF 0.14 · pLI 1.00 · ClinGen HI 3/3 (gnomAD)
Structure: AlphaFold pLDDT 92.75 · 5 PDB

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

Disease context

neurodevelopmental disorder — disease report on Sugi Atlas → Associated genes, phenotypes, clinical trials & treatments

Similar variants

NCKAP1 c.1004+1G>A Pathogenic ★ same condition
NCKAP1 p.Tyr496Ter Pathogenic ★ same condition
NCKAP1 p.Gln758Arg Uncertain significance ★ ⚠ same condition
NCKAP1 p.Gly362Ala Likely benign ★ ⚠ same condition
NCKAP1 p.Ala1115_Tyr1116insTer Uncertain significance ★ same condition
NCKAP1 p.Arg798Ter Pathogenic ★★ same type
NCKAP1 p.Ala1128Val Uncertain significance ★★ ⚠ same type
NCKAP1 p.Arg1054His Uncertain significance ★★ ⚠ same type

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-arg669ser (accessed [today's date]).

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