Is CP p.Gln1004Arg (c.3011A>G) pathogenic?

CP p.Gln1004Arg (c.3011A>G) is classified Uncertain significance in CP (ClinVar, Single submitter, 1 submitter; last evaluated 2019-07-11). AlphaMissense: likely benign (0.0554); Very rare (popmax 6.84e-05%).

How common is CP p.Gln1004Arg (c.3011A>G) in the general population?

CP p.Gln1004Arg (c.3011A>G) is very rare (popmax 6.84e-05%) (gnomAD).

What do computational predictors say about CP p.Gln1004Arg (c.3011A>G)?

AlphaMissense predicts likely benign (score 0.0554) — an in-silico prediction, not a clinical call.

CP p.Gln1004Arg

c.3011A>G · rs2108214389 · VCV1198134

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.0554 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 6.84e-05%)

Missense predictors

0/3 damaging

AlphaMissense, REVEL, SaProt

Computational evidence

Protein change
AlphaMissense	0.0554	likely benign
REVEL	0.283	benign-leaning
SaProt	LLR -5.08	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 -4.8	GERP -3.9
Regional constraint	o/e 0.80	unconstrained · MANE · 25 kb · p 2.5e-07 · regional, not allelic
Overall
CADD	0.237	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 6.84e-05%

Overall 6.84e-05% 1/1,461,464 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.Gln1004Arg
Coding: c.3011A>G
MANE Select: NM_000096
dbSNP: rs2108214389
Type: single nucleotide variant
Location: chr3:149177847 (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 1004: a β-strand; the plastocyanin-like 6 domain

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

Similar variants

HPS3 p.Thr1004= Likely benign ★ same residue
HPS3 p.Thr1004Ile Uncertain significance ⚠ same residue
CP c.1208+1G>A Pathogenic ★★ same type
CP c.2879-1G>T Likely pathogenic ★★ same type
CP p.Arg901Ter Pathogenic ★★ same type
CP p.Gly195Arg Likely pathogenic ★★ same type
CP p.Gly650Arg Pathogenic/Likely pathogenic ★★ same type
CP p.Gly708Ser 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-gln1004arg (accessed [today's date]).

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