Is NCKAP1 p.Ser752Ala (c.2254T>G) pathogenic?

NCKAP1 p.Ser752Ala (c.2254T>G) is classified Uncertain significance in NCKAP1 (ClinVar, Single submitter, 1 submitter; last evaluated 2026-02-17). AlphaMissense: likely benign (0.2096); Absent from gnomAD v4.1; Associated with Inborn genetic diseases.

What condition is associated with NCKAP1 p.Ser752Ala (c.2254T>G)?

NCKAP1 p.Ser752Ala (c.2254T>G) is associated with Inborn genetic diseases (ClinVar).

How common is NCKAP1 p.Ser752Ala (c.2254T>G) in the general population?

NCKAP1 p.Ser752Ala (c.2254T>G) is absent from gnomAD v4.1 (gnomAD).

What do computational predictors say about NCKAP1 p.Ser752Ala (c.2254T>G)?

AlphaMissense predicts likely benign (score 0.2096) — an in-silico prediction, not a clinical call.

NCKAP1 p.Ser752Ala

c.2254T>G · VCV4840038

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.2096 · ACMG-weighted

gnomAD v4.1

Absent

absent from gnomAD v4.1

Missense predictors

0/3 damaging

AlphaMissense, REVEL, SaProt

Conditions

Inborn genetic diseases

Computational evidence

Protein change
AlphaMissense	0.2096	likely benign
REVEL	0.255	benign-leaning
SaProt	LLR -7.94	tolerated
⇒ AlphaMissense, REVEL and SaProt all call this tolerated.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 11	GERP 2.1, phastCons 1
Regional constraint	o/e 0.59	unconstrained · MANE · 32 kb · p 1.2e-22 · regional, not allelic
Overall
CADD	27.1	PHRED · no single calibrated threshold — expert panels disagree

ClinVar classifies this uncertain; the computational predictors unanimously lean tolerated — 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

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.Ser752Ala
Coding: c.2254T>G
MANE Select: NM_013436
Type: single nucleotide variant
Location: chr2:182953231 (GRCh38)
Gene constraint: LOEUF 0.14 · pLI 1.00 · ClinGen HI 3/3 (gnomAD)
Structure: AlphaFold pLDDT 92.75 · 5 PDB
Residue 752: an α-helix

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

Disease context

Inborn genetic diseases — disease report on Sugi Atlas → Associated genes, phenotypes, clinical trials & treatments

Similar variants

NCKAP1 p.Arg1054His Uncertain significance ★★ ⚠ same condition
NCKAP1 p.Cys327Arg Uncertain significance ★★ ⚠ same condition
NCKAP1 p.Glu15Gly Uncertain significance ★★ ⚠ same condition
NCKAP1 p.Ile689Val Uncertain significance ★★ ⚠ same condition
NCKAP1 p.Leu268Phe Uncertain significance ★★ ⚠ same condition
NCKAP1 p.Met665Ile Uncertain significance ★★ ⚠ same condition
NCKAP1 p.Met695Ile Uncertain significance ★★ ⚠ same condition
NCKAP1 p.Val431Leu 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-ser752ala (accessed [today's date]).

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