Is CTAGE6 p.Ala321Pro (c.961G>C) pathogenic?

CTAGE6 p.Ala321Pro (c.961G>C) is classified Uncertain significance in CTAGE6 (ClinVar, Single submitter, 1 submitter; last evaluated 2024-06-13). AlphaMissense: likely pathogenic (0.6188); Very rare (popmax 0.0057%, amr).

How common is CTAGE6 p.Ala321Pro (c.961G>C) in the general population?

CTAGE6 p.Ala321Pro (c.961G>C) is very rare (popmax 0.0057%, amr) (gnomAD).

What do computational predictors say about CTAGE6 p.Ala321Pro (c.961G>C)?

AlphaMissense predicts likely pathogenic (score 0.6188) — an in-silico prediction, not a clinical call.

CTAGE6 p.Ala321Pro

c.961G>C · VCV3270013

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely pathogenic

0.6188 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 0.0057%, amr)

Missense predictors

2/2 damaging

AlphaMissense, SaProt

Computational evidence

Protein change
AlphaMissense	0.6188	likely pathogenic · top 2% in CTAGE6
SaProt	LLR -11.98	damaging
⇒ AlphaMissense and SaProt both call this damaging.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 0.68	GERP 2.5
Regional constraint	o/e 0.01	constrained · MANE · 1,062 bp · p 1.2e-45 · regional, not allelic
Overall
CADD	18.28	PHRED · no single calibrated threshold — expert panels disagree

ClinVar classifies this uncertain; the computational predictors unanimously lean damaging — 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 0.0057% Admixed American · 3/52,656 alleles

Filtering AF 0.00151% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.000819%

Overall 0.000765% 12/1,568,306 alleles · very rare

Ancestry group	Frequency	1 in
Admixed Americangrpmax	0.0057%	17,552
Remaining individualsnot grpmax-eligible	0.00494%	20,238
South Asian	0.00118%	85,026
European (non-Finnish)	0.000432%	231,623

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.Ala321Pro
Coding: c.961G>C
MANE Select: NM_178561
Type: single nucleotide variant
Location: chr7:143756698 (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.Glu364Ala Benign ★★ 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
CTAGE6 p.Arg126Gln Uncertain significance ★ ⚠ same type
CTAGE6 p.Arg204Gln 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-ala321pro (accessed [today's date]).

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