Is NCKAP1 p.Ser918Pro (c.2752T>C) pathogenic?

NCKAP1 p.Ser918Pro (c.2752T>C) is classified Uncertain significance in NCKAP1 (ClinVar, Single submitter, 1 submitter; last evaluated 2025-04-29). AlphaMissense: likely pathogenic (0.9858); No allele count reported in gnomAD v4.1 (AN 1,592,358).

How common is NCKAP1 p.Ser918Pro (c.2752T>C) in the general population?

NCKAP1 p.Ser918Pro (c.2752T>C) is no allele count reported in gnomAD v4.1 (AN 1,592,358) (gnomAD).

What do computational predictors say about NCKAP1 p.Ser918Pro (c.2752T>C)?

AlphaMissense predicts likely pathogenic (score 0.9858) — an in-silico prediction, not a clinical call.

NCKAP1 p.Ser918Pro

c.2752T>C · VCV4527017

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely pathogenic

0.9858 · ACMG-weighted

gnomAD v4.1

Not reported

no allele count reported in gnomAD v4.1 (AN 1,592,358)

Missense predictors

2/2 damaging

AlphaMissense, SaProt · REVEL indeterminate

Computational evidence

Protein change
AlphaMissense	0.9858	likely pathogenic
REVEL	0.399	indeterminate
SaProt	LLR -13.41	damaging
⇒ AlphaMissense and SaProt both call this damaging; REVEL is indeterminate.
Splicing
SpliceAI	<0.2	no splice effect predicted · four deltas, not one · how we know
Constraint at this position
Conservation	phyloP 11	GERP 2, phastCons 1
Regional constraint	o/e 0.59	unconstrained · MANE · 32 kb · p 1.2e-22 · regional, not allelic
Overall
CADD	26.9	PHRED · no single calibrated threshold — expert panels disagree

ClinVar classifies this uncertain; the computational predictors unanimously lean damaging — a triage signal, not a reclassification

AlphaMissense carries the ACMG weight for missense; REVEL and SaProt are independent agreement signals.

Population frequency

gnomAD v4.1 · exomes + genomes

No allele count reported in gnomAD v4.1 (AN 1,592,358). 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.Ser918Pro
Coding: c.2752T>C
MANE Select: NM_013436
Type: single nucleotide variant
Location: chr2:182935319 (GRCh38)
Gene constraint: LOEUF 0.14 · pLI 1.00 · ClinGen HI 3/3 (gnomAD)
Structure: AlphaFold pLDDT 92.75 · 5 PDB
Residue 918: an α-helix

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

Similar variants

NCKAP1 p.Arg798Ter Pathogenic ★★ same type
NCKAP1 p.Ala1128Val Uncertain significance ★★ ⚠ same type
NCKAP1 p.Arg1054His Uncertain significance ★★ ⚠ same type
NCKAP1 p.Cys327Arg Uncertain significance ★★ ⚠ same type
NCKAP1 p.Glu15Gly Uncertain significance ★★ ⚠ same type
NCKAP1 p.Ile689Val Uncertain significance ★★ ⚠ same type
NCKAP1 p.Leu268Phe Uncertain significance ★★ ⚠ same type
NCKAP1 p.Met665Ile 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-ser918pro (accessed [today's date]).

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