Is CTAGE15 p.Arg69Trp (c.205C>T) pathogenic?

CTAGE15 p.Arg69Trp (c.205C>T) is classified Uncertain significance in CTAGE15 (ClinVar, Single submitter, 1 submitter; last evaluated 2025-08-07). AlphaMissense: likely benign (0.1289); Ultra-rare (popmax 0.0329%, mid).

How common is CTAGE15 p.Arg69Trp (c.205C>T) in the general population?

CTAGE15 p.Arg69Trp (c.205C>T) is ultra-rare (popmax 0.0329%, mid) (gnomAD).

What do computational predictors say about CTAGE15 p.Arg69Trp (c.205C>T)?

AlphaMissense predicts likely benign (score 0.1289) — an in-silico prediction, not a clinical call.

CTAGE15 p.Arg69Trp

c.205C>T · VCV4235448

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.1289 · ACMG-weighted

gnomAD v4.1

Rare

ultra-rare (popmax 0.0329%, mid)

Missense predictors

0/2 damaging

AlphaMissense, SaProt

Computational evidence

Protein change
AlphaMissense	0.1289	likely benign
SaProt	LLR -6.80	tolerated
⇒ AlphaMissense and SaProt both call this tolerated.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP -4.5	GERP -6
Regional constraint	o/e 0.01	constrained · MANE · 1,155 bp · p 1.1e-54 · regional, not allelic
Overall
CADD	14.98	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 0.0329% Middle Eastern · 1/3,044 alleles

Filtering AF 0.000125% ClinGen BA1/BS1 input FAF95, joint · FAF99 3.5e-05%

Overall 0.000477% 4/838,664 alleles · ultra-rare

Ancestry group	Frequency	1 in
Middle Easterngrpmax	0.0329%	3,044
European (non-Finnish)	0.000468%	213,828

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: CTAGE15
Protein: p.Arg69Trp
Coding: c.205C>T
MANE Select: NM_001008747
Type: single nucleotide variant
Location: chr7:143572022 (GRCh38)
Gene constraint: LOEUF 0.7 · pLI 0.80 (gnomAD)
Structure: AlphaFold pLDDT 69.60

Full CTAGE15 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Similar variants

CTAGE15 p.Ala437Ser Uncertain significance ★ ⚠ same type
CTAGE15 p.Arg425Cys Uncertain significance ★ ⚠ same type
CTAGE15 p.Arg425Leu Uncertain significance ★ ⚠ same type
CTAGE15 p.Arg470Trp Uncertain significance ★ ⚠ same type
CTAGE15 p.Asn242Ser Uncertain significance ★ ⚠ same type
CTAGE15 p.Asn394Asp Uncertain significance ★ ⚠ same type
CTAGE15 p.Asn486Thr Uncertain significance ★ ⚠ same type
CTAGE15 p.Asp211His 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/ctage15-p-arg69trp (accessed [today's date]).

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