Is CTAGE1 p.Arg669Ser (c.2007A>C) pathogenic?

CTAGE1 p.Arg669Ser (c.2007A>C) is classified Uncertain significance in CTAGE1 (ClinVar, Single submitter, 1 submitter; last evaluated 2025-02-22). AlphaMissense: likely benign (0.2614); Ultra-rare (popmax 0.0329%, mid).

How common is CTAGE1 p.Arg669Ser (c.2007A>C) in the general population?

CTAGE1 p.Arg669Ser (c.2007A>C) is ultra-rare (popmax 0.0329%, mid) (gnomAD).

What do computational predictors say about CTAGE1 p.Arg669Ser (c.2007A>C)?

AlphaMissense predicts likely benign (score 0.2614) — an in-silico prediction, not a clinical call.

CTAGE1 p.Arg669Ser

c.2007A>C · rs762214213 · VCV2397292

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.2614 · ACMG-weighted

gnomAD v4.1

Rare

ultra-rare (popmax 0.0329%, mid)

Missense predictors

0/3 damaging

AlphaMissense, REVEL, SaProt

Computational evidence

Protein change
AlphaMissense	0.2614	likely benign
REVEL	0.036	moderately benign-leaning
SaProt	LLR -6.99	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 0.88	GERP -2.4, phastCons 0.024
Regional constraint	o/e 1.13	unconstrained · MANE · 2,234 bp · p 0.00025 · regional, not allelic
Overall
CADD	11.98	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 · 2/6,078 alleles

Filtering AF 0.0207% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.0172%

Overall 0.00397% 64/1,613,754 alleles · ultra-rare

Ancestry group	Frequency	1 in
Middle Easterngrpmax	0.0329%	3,039
Admixed American	0.0317%	3,157
South Asian	0.0187%	5,357
Remaining individualsnot grpmax-eligible	0.00961%	10,411
East Asian	0.00891%	11,222
African / African-American	0.00134%	74,878
European (non-Finnish)	0.00127%	78,657

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: CTAGE1
Protein: p.Arg669Ser
Coding: c.2007A>C
MANE Select: NM_172241
dbSNP: rs762214213
Type: single nucleotide variant
Location: chr18:22415805 (GRCh38)
Structure: AlphaFold pLDDT 70.45

Full CTAGE1 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Similar variants

CTAGE1 p.Ala169= Benign ★★ same type
CTAGE1 p.Ile682Met Benign ★★ same type
CTAGE1 p.Pro686Thr Benign ★★ ⚠ same type
CTAGE1 p.Val696Met Benign ★★ same type
CTAGE1 p.Ala181Val Uncertain significance ★ ⚠ same type
CTAGE1 p.Ala19Thr Uncertain significance ★ ⚠ same type
CTAGE1 p.Ala282Asp Uncertain significance ★ ⚠ same type
CTAGE1 p.Ala332Thr 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/ctage1-p-arg669ser (accessed [today's date]).

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