Is CP p.Ser955Asn (c.2864G>A) pathogenic?

CP p.Ser955Asn (c.2864G>A) is classified Uncertain significance in CP (ClinVar, Single submitter, 1 submitter; last evaluated 2025-11-05). AlphaMissense: ambiguous (0.5213); Very rare (popmax 0.00893%, eas); Associated with Inborn genetic diseases.

What condition is associated with CP p.Ser955Asn (c.2864G>A)?

CP p.Ser955Asn (c.2864G>A) is associated with Inborn genetic diseases (ClinVar).

How common is CP p.Ser955Asn (c.2864G>A) in the general population?

CP p.Ser955Asn (c.2864G>A) is very rare (popmax 0.00893%, eas) (gnomAD).

What do computational predictors say about CP p.Ser955Asn (c.2864G>A)?

AlphaMissense predicts ambiguous (score 0.5213) — an in-silico prediction, not a clinical call.

CP p.Ser955Asn

c.2864G>A · rs1725556395 · VCV2618956

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

ambiguous

0.5213 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 0.00893%, eas)

Conditions

Inborn genetic diseases

Computational evidence

Protein change
AlphaMissense	0.5213	ambiguous
REVEL	0.632	indeterminate
SaProt	LLR -9.67	tolerated
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 7.7	GERP 2.2, phastCons 1
Regional constraint	o/e 0.80	unconstrained · MANE · 25 kb · p 2.5e-07 · regional, not allelic
Overall
CADD	24.0	PHRED · no single calibrated threshold — expert panels disagree

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

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.00893% East Asian · 4/44,792 alleles

Filtering AF 0.00298% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.0018%

Overall 0.000344% 5/1,455,394 alleles · very rare

Ancestry group	Frequency	1 in
East Asiangrpmax	0.00893%	11,198
Admixed American	0.00167%	59,902

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.Ser955Asn
Coding: c.2864G>A
MANE Select: NM_000096
dbSNP: rs1725556395
Type: single nucleotide variant
Location: chr3:149178429 (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 955: an α-helix; a binding site; the plastocyanin-like 6 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

HPS3 p.Gln955= Likely benign ★ same residue
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

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-ser955asn (accessed [today's date]).

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