Is CTAGE6 p.Ser299Arg (c.895A>C) pathogenic?

CTAGE6 p.Ser299Arg (c.895A>C) is classified Uncertain significance in CTAGE6 (ClinVar, Single submitter, 1 submitter; last evaluated 2025-04-03). AlphaMissense: likely benign (0.209); Very rare (popmax 0.00845%, afr).

How common is CTAGE6 p.Ser299Arg (c.895A>C) in the general population?

CTAGE6 p.Ser299Arg (c.895A>C) is very rare (popmax 0.00845%, afr) (gnomAD).

What do computational predictors say about CTAGE6 p.Ser299Arg (c.895A>C)?

AlphaMissense predicts likely benign (score 0.209) — an in-silico prediction, not a clinical call.

CTAGE6 p.Ser299Arg

c.895A>C · VCV4007829

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.209 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 0.00845%, afr)

Missense predictors

0/2 damaging

AlphaMissense, SaProt

Computational evidence

Protein change
AlphaMissense	0.209	likely benign
SaProt	LLR -7.31	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 1.6	GERP -0.072, phastCons 0.031
Regional constraint	o/e 0.01	constrained · MANE · 1,062 bp · p 1.2e-45 · regional, not allelic
Overall
CADD	12.73	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 0.00845% African / African-American · 6/70,996 alleles

Filtering AF 0.00363% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.00249%

Overall 0.000391% 6/1,533,638 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.Ser299Arg
Coding: c.895A>C
MANE Select: NM_178561
Type: single nucleotide variant
Location: chr7:143756764 (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.Ser299Asn 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.Ala484Pro Uncertain significance ★ ⚠ same type
CTAGE6 p.Ala484Val 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-ser299arg (accessed [today's date]).

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