Is CTAGE9 p.Glu414Asp (c.1242G>T) pathogenic?

CTAGE9 p.Glu414Asp (c.1242G>T) is classified Uncertain significance in CTAGE9 (ClinVar, Single submitter, 1 submitter; last evaluated 2025-08-21). AlphaMissense: likely benign (0.1806); Very rare (popmax 0.00223%, eas).

How common is CTAGE9 p.Glu414Asp (c.1242G>T) in the general population?

CTAGE9 p.Glu414Asp (c.1242G>T) is very rare (popmax 0.00223%, eas) (gnomAD).

What do computational predictors say about CTAGE9 p.Glu414Asp (c.1242G>T)?

AlphaMissense predicts likely benign (score 0.1806) — an in-silico prediction, not a clinical call.

CTAGE9 p.Glu414Asp

c.1242G>T · VCV4235480

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.1806 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 0.00223%, eas)

Missense predictors

0/3 damaging

AlphaMissense, REVEL, SaProt

Computational evidence

Protein change
AlphaMissense	0.1806	likely benign
REVEL	0.176	moderately benign-leaning
SaProt	LLR -7.56	tolerated
⇒ AlphaMissense, REVEL and SaProt all call this tolerated.
Splicing
SpliceAI	—	not looked up on this page · why
Constraint at this position
Conservation	phyloP -0.44	GERP -2.3, phastCons 0.076
Regional constraint	o/e 0.66	unconstrained · MANE · 222 bp · p 0.0021 · regional, not allelic
Overall
CADD	16.38	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 · 1/44,852 alleles

Overall 6.84e-05% 1/1,461,604 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: CTAGE9
Protein: p.Glu414Asp
Coding: c.1242G>T
MANE Select: NM_005021 · reported on NM_001145659
Type: single nucleotide variant
Location: chr6:131709776 (GRCh38)

Full CTAGE9 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

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/ctage9-p-glu414asp (accessed [today's date]).

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