Is CP p.Asn596Lys (c.1788T>A) pathogenic?

CP p.Asn596Lys (c.1788T>A) is classified Uncertain significance in CP (ClinVar, Single submitter, 1 submitter; last evaluated 2025-04-30). AlphaMissense: likely pathogenic (0.9756); Very rare (popmax 6.85e-05%); Associated with Inborn genetic diseases.

What condition is associated with CP p.Asn596Lys (c.1788T>A)?

CP p.Asn596Lys (c.1788T>A) is associated with Inborn genetic diseases (ClinVar).

How common is CP p.Asn596Lys (c.1788T>A) in the general population?

CP p.Asn596Lys (c.1788T>A) is very rare (popmax 6.85e-05%) (gnomAD).

What do computational predictors say about CP p.Asn596Lys (c.1788T>A)?

AlphaMissense predicts likely pathogenic (score 0.9756) — an in-silico prediction, not a clinical call.

CP p.Asn596Lys

c.1788T>A · VCV4006030

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely pathogenic

0.9756 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 6.85e-05%)

Missense predictors

3/3 damaging

AlphaMissense, REVEL, SaProt

Conditions

Inborn genetic diseases

Computational evidence

Protein change
AlphaMissense	0.9756	likely pathogenic · top 2% in CP
REVEL	0.791	moderately pathogenic-leaning
SaProt	LLR -14.07	damaging
⇒ AlphaMissense, REVEL and SaProt all call this damaging.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 0.86	GERP -2.9, phastCons 0.99
Regional constraint	o/e 0.80	unconstrained · MANE · 25 kb · p 2.5e-07 · regional, not allelic
Overall
CADD	21.0	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

Grpmax group 6.85e-05%

Overall 6.85e-05% 1/1,460,570 alleles · very rare

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: CP
Protein: p.Asn596Lys
Coding: c.1788T>A
MANE Select: NM_000096
Type: single nucleotide variant
Location: chr3:149188128 (GRCh38)
Gene constraint: LOEUF 0.624 · pLI <0.01 · ClinGen HI gene assoc. with recessive phenotype (gnomAD)
Structure: AlphaFold pLDDT 93.79 · 4 PDB
Residue 596: an α-helix; the plastocyanin-like 4 domain

Full CP 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

CP p.Asn397Lys Uncertain significance ★★ ⚠ same condition
CP p.Asp654Asn Uncertain significance ★★ ⚠ same condition
CP p.Glu742Gln Uncertain significance ★★ ⚠ same condition
CP p.Glu754Lys Uncertain significance ★★ ⚠ same condition
CP p.Glu803Gln Uncertain significance ★★ ⚠ same condition
CP p.Gly730Val Uncertain significance ★★ ⚠ same condition
CP p.Gly967Ala Uncertain significance ★★ ⚠ same condition
CP p.His445Tyr 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/cp-p-asn596lys (accessed [today's date]).

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