Is CTAGE6 p.Ala484Pro (c.1450G>C) pathogenic?

CTAGE6 p.Ala484Pro (c.1450G>C) is classified Uncertain significance in CTAGE6 (ClinVar, Single submitter, 1 submitter; last evaluated 2024-10-08). AlphaMissense: likely pathogenic (0.7356); Very rare (popmax 0.000606%, nfe).

How common is CTAGE6 p.Ala484Pro (c.1450G>C) in the general population?

CTAGE6 p.Ala484Pro (c.1450G>C) is very rare (popmax 0.000606%, nfe) (gnomAD).

What do computational predictors say about CTAGE6 p.Ala484Pro (c.1450G>C)?

AlphaMissense predicts likely pathogenic (score 0.7356) — an in-silico prediction, not a clinical call.

CTAGE6 p.Ala484Pro

c.1450G>C · rs1229292199 · VCV2284337

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely pathogenic

0.7356 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 0.000606%, nfe)

Missense predictors

2/2 damaging

AlphaMissense, SaProt

Computational evidence

Protein change
AlphaMissense	0.7356	likely pathogenic · top 1% in CTAGE6
SaProt	LLR -11.70	damaging
⇒ AlphaMissense and SaProt both call this damaging.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP -0.1	GERP -0.47
Regional constraint	o/e 0.06	constrained · MANE · 975 bp · p 7.2e-25 · regional, not allelic
Overall
CADD	20.9	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 0.000606% European (non-Finnish) · 7/1,155,542 alleles

Filtering AF 0.000252% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.000162%

Overall 0.000493% 7/1,420,036 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: CTAGE6
Protein: p.Ala484Pro
Coding: c.1450G>C
MANE Select: NM_178561
dbSNP: rs1229292199
Type: single nucleotide variant
Location: chr7:143756209 (GRCh38)
Gene constraint: LOEUF 0.345 · pLI 1.00 (gnomAD)
Structure: AlphaFold pLDDT 69.68

Full CTAGE6 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Similar variants

CTAGE6 p.Ala484Val Uncertain significance ★ ⚠ same residue
CTAGE6 p.Glu364Ala Benign ★★ same type
CTAGE6 p.Ala321Pro Uncertain significance ★ ⚠ same type
CTAGE6 p.Ala322Gly Uncertain significance ★ ⚠ same type
CTAGE6 p.Ala322Val Uncertain significance ★ ⚠ same type
CTAGE6 p.Ala437Thr Uncertain significance ★ ⚠ same type
CTAGE6 p.Arg126Gln Uncertain significance ★ ⚠ same type
CTAGE6 p.Arg204Gln Uncertain significance ★ ⚠ 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/ctage6-p-ala484pro (accessed [today's date]).

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