Is CTAGE9 p.Pro4Ala (c.10C>G) pathogenic?

CTAGE9 p.Pro4Ala (c.10C>G) is classified Uncertain significance in CTAGE9 (ClinVar, Single submitter, 1 submitter; last evaluated 2022-01-05). AlphaMissense: likely benign (0.0722); Very rare (popmax 0.00177%, amr).

How common is CTAGE9 p.Pro4Ala (c.10C>G) in the general population?

CTAGE9 p.Pro4Ala (c.10C>G) is very rare (popmax 0.00177%, amr) (gnomAD).

What do computational predictors say about CTAGE9 p.Pro4Ala (c.10C>G)?

AlphaMissense predicts likely benign (score 0.0722) — an in-silico prediction, not a clinical call.

CTAGE9 p.Pro4Ala

c.10C>G · rs1779775352 · VCV2270513

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.0722 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 0.00177%, amr)

Missense predictors

0/3 damaging

AlphaMissense, REVEL, SaProt

Computational evidence

Protein change
AlphaMissense	0.0722	likely benign
REVEL	0.028	moderately benign-leaning
SaProt	LLR -5.24	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 0.48	GERP -3.3
Regional constraint	o/e 0.58	unconstrained · MANE · 262 bp · p 2.1e-05 · regional, not allelic
Overall
CADD	7.173	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 0.00177% Admixed American · 1/56,418 alleles

Overall 0.000189% 3/1,590,712 alleles · very rare

Ancestry group	Frequency	1 in
Finnishnot grpmax-eligible	0.00313%	31,904
Admixed Americangrpmax	0.00177%	56,418

Finnish shows a higher raw frequency than the grpmax group above it. gnomAD excludes bottlenecked groups — Finnish, Ashkenazi Jewish, Amish and “Remaining individuals” — from grpmax, because founder effects make their frequencies unrepresentative for filtering. The table is sorted by frequency, so an excluded group can sit above the grpmax row.

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.Pro4Ala
Coding: c.10C>G
MANE Select: NM_001145659
dbSNP: rs1779775352
Type: single nucleotide variant
Location: chr6:131711008 (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-pro4ala (accessed [today's date]).

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