Is CP p.Val996Ala (c.2987T>C) pathogenic?

CP p.Val996Ala (c.2987T>C) is classified Uncertain significance in CP (ClinVar, No assertion criteria, 1 submitter; last evaluated 2023-12-12). AlphaMissense: likely benign (0.1812); Very rare (popmax 0.00223%, eas); Associated with CP-related disorder.

What condition is associated with CP p.Val996Ala (c.2987T>C)?

CP p.Val996Ala (c.2987T>C) is associated with CP-related disorder (ClinVar).

How common is CP p.Val996Ala (c.2987T>C) in the general population?

CP p.Val996Ala (c.2987T>C) is very rare (popmax 0.00223%, eas) (gnomAD).

What do computational predictors say about CP p.Val996Ala (c.2987T>C)?

AlphaMissense predicts likely benign (score 0.1812) — an in-silico prediction, not a clinical call.

CP p.Val996Ala

c.2987T>C · rs774951664 · VCV3028982

Uncertain significance No assertion criteria

Classification

Uncertain significance

ClinVar

Review

No assertion criteria ☆☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.1812 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 0.00223%, eas)

Missense predictors

0/2 damaging

AlphaMissense, SaProt · REVEL no call

Conditions

CP-related disorder

Computational evidence

Protein change
AlphaMissense	0.1812	likely benign
REVEL	0.566	indeterminate
SaProt	LLR -8.80	tolerated
⇒ AlphaMissense and SaProt both call this tolerated; REVEL makes no call.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 7.1	GERP 2.1, phastCons 1
Regional constraint	o/e 0.80	unconstrained · MANE · 25 kb · p 2.5e-07 · regional, not allelic
Overall
CADD	18.79	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

Grpmax group 0.00223% East Asian · 1/44,886 alleles

Filtering AF 7.9e-05% ClinGen BA1/BS1 input FAF95, joint · FAF99 5.4e-05%

Overall 0.00031% 5/1,613,690 alleles · very rare

Ancestry group	Frequency	1 in
East Asiangrpmax	0.00223%	44,886
European (non-Finnish)	0.000339%	294,930

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.Val996Ala
Coding: c.2987T>C
MANE Select: NM_000096
dbSNP: rs774951664
Type: single nucleotide variant
Location: chr3:149177871 (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 996: a β-strand; the plastocyanin-like 6 domain

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

Disease context

CP-related disorder

Similar variants

HPS3 p.Tyr996Cys Uncertain significance ★ ⚠ same residue
HPS3 p.Tyr996= Likely benign ★ same residue
CP p.Ser121Ter Likely pathogenic ★ same condition
CP p.Trp230Ter Pathogenic ★ same condition
CP p.Trp644Ter Likely pathogenic ★ same condition
CP p.Lys753Ter Likely pathogenic same condition
CP p.Tyr1011Ter Pathogenic same condition
CP p.Cys13= Likely benign 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-val996ala (accessed [today's date]).

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