Is CTAGE9 p.Trp234Arg (c.700T>C) pathogenic?

CTAGE9 p.Trp234Arg (c.700T>C) is classified Uncertain significance in CTAGE9 (ClinVar, Single submitter, 1 submitter; last evaluated 2025-03-01). AlphaMissense: likely pathogenic (0.5919); Ultra-rare (popmax 0.0117%, eas).

How common is CTAGE9 p.Trp234Arg (c.700T>C) in the general population?

CTAGE9 p.Trp234Arg (c.700T>C) is ultra-rare (popmax 0.0117%, eas) (gnomAD).

What do computational predictors say about CTAGE9 p.Trp234Arg (c.700T>C)?

AlphaMissense predicts likely pathogenic (score 0.5919) — an in-silico prediction, not a clinical call.

CTAGE9 p.Trp234Arg

c.700T>C · VCV3837070

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely pathogenic

0.5919 · ACMG-weighted

gnomAD v4.1

Rare

ultra-rare (popmax 0.0117%, eas)

Missense predictors

1/3 damaging

AlphaMissense, REVEL, SaProt

Computational evidence

Protein change
AlphaMissense	0.5919	likely pathogenic · top 2% in CTAGE9
REVEL	0.085	moderately benign-leaning
SaProt	LLR -7.10	tolerated
⇒ AlphaMissense calls this damaging; REVEL and SaProt do not.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 0.94	GERP -3.4
Regional constraint	o/e 0.03	constrained · MANE · 294 bp · p 9.7e-25 · regional, not allelic
Overall
CADD	16.77	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 0.0117% East Asian · 5/42,902 alleles

Filtering AF 0.00451% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.00297%

Overall 0.00045% 7/1,556,944 alleles · ultra-rare

Ancestry group	Frequency	1 in
East Asiangrpmax	0.0117%	8,580
Admixed American	0.00196%	51,050
Remaining individualsnot grpmax-eligible	0.00166%	60,414

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.Trp234Arg
Coding: c.700T>C
MANE Select: NM_001145659
Type: single nucleotide variant
Location: chr6:131710318 (GRCh38)
Gene constraint: LOEUF 1.713 · pLI 0.41 (gnomAD)
Structure: AlphaFold pLDDT 69.37

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

Similar variants

CTAGE9 p.Ala120Thr Uncertain significance ★ ⚠ same type
CTAGE9 p.Ala120Val Uncertain significance ★ ⚠ same type
CTAGE9 p.Ala122Val Uncertain significance ★ ⚠ same type
CTAGE9 p.Ala168Val Uncertain significance ★ ⚠ same type
CTAGE9 p.Ala208Val Uncertain significance ★ ⚠ same type
CTAGE9 p.Ala280Val Uncertain significance ★ ⚠ same type
CTAGE9 p.Ala321Thr Uncertain significance ★ ⚠ same type
CTAGE9 p.Ala48Pro 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/ctage9-p-trp234arg (accessed [today's date]).

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