Is CP p.Trp644Ter (c.1931G>A) pathogenic?

CP p.Trp644Ter (c.1931G>A) is classified Likely pathogenic in CP (ClinVar, Single submitter, 1 submitter; last evaluated 2023-04-02). Very rare (popmax 0.0011%, nfe); Associated with CP-related disorder.

What condition is associated with CP p.Trp644Ter (c.1931G>A)?

CP p.Trp644Ter (c.1931G>A) is associated with CP-related disorder (ClinVar).

How common is CP p.Trp644Ter (c.1931G>A) in the general population?

CP p.Trp644Ter (c.1931G>A) is very rare (popmax 0.0011%, nfe) (gnomAD).

CP p.Trp644Ter

c.1931G>A · rs1361931808 · VCV2628606

Likely pathogenic Single submitter

Classification

Likely pathogenic

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

Consequence

nonsense (stop-gain)

predicted LoF

gnomAD v4.1

Rare

very rare (popmax 0.0011%, nfe)

Conditions

CP-related disorder

Computational evidence

Protein change
Missense predictors do not apply to this variant type; conservation carries the signal.
Consequence	nonsense (stop-gain)	predicted loss-of-function
NMD	predicted	premature termination codon in exon 11 of 19
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 7.7	GERP 2.2, phastCons 1
Overall
CADD	42.0	PHRED · no single calibrated threshold — expert panels disagree

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

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.0011% European (non-Finnish) · 13/1,180,022 alleles

Filtering AF 0.000615% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.000474%

Overall 0.000805% 13/1,614,010 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.Trp644Ter
Coding: c.1931G>A
MANE Select: NM_000096
dbSNP: rs1361931808
Type: single nucleotide variant
Location: chr3:149186666 (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 644: a β-strand; the plastocyanin-like 4 domain; a disulfide bond

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

Disease context

CP-related disorder

Similar variants

CP p.Ser121Ter Likely pathogenic ★ same condition
CP p.Trp230Ter Pathogenic ★ same condition
CP p.Lys753Ter Likely pathogenic same condition
CP p.Tyr1011Ter Pathogenic same condition
CP p.Val996Ala Uncertain significance ⚠ same condition
CP p.Cys13= Likely benign same condition
CP p.Glu380fs Likely pathogenic ★ same condition
CP c.1208+1G>A Pathogenic ★★ 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/cp-p-trp644ter (accessed [today's date]).

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