Is CTU1 p.Pro19Leu (c.56C>T) pathogenic?

CTU1 p.Pro19Leu (c.56C>T) is classified Uncertain significance in CTU1 (ClinVar, Single submitter, 1 submitter; last evaluated 2021-08-30). AlphaMissense: ambiguous (0.4829); Very rare (popmax 0.00624%, eas).

How common is CTU1 p.Pro19Leu (c.56C>T) in the general population?

CTU1 p.Pro19Leu (c.56C>T) is very rare (popmax 0.00624%, eas) (gnomAD).

What do computational predictors say about CTU1 p.Pro19Leu (c.56C>T)?

AlphaMissense predicts ambiguous (score 0.4829) — an in-silico prediction, not a clinical call.

CTU1 p.Pro19Leu

c.56C>T · rs562481846 · VCV2228749

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

ambiguous

0.4829 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 0.00624%, eas)

Computational evidence

Protein change
AlphaMissense	0.4829	ambiguous
REVEL	0.357	indeterminate
SaProt	LLR -8.66	tolerated
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 6.8	GERP 0.85, phastCons 1
Regional constraint	o/e 1.09	unconstrained · MANE · 5,790 bp · p 0.053 · regional, not allelic
Overall
CADD	25.7	PHRED · no single calibrated threshold — expert panels disagree

AlphaMissense carries the ACMG weight for missense; REVEL and SaProt are independent agreement signals.

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.00624% East Asian · 2/32,028 alleles

Filtering AF 0.00133% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.00113%

Overall 0.0018% 23/1,276,300 alleles · very rare

Ancestry group	Frequency	1 in
East Asiangrpmax	0.00624%	16,014
European (non-Finnish)	0.00207%	48,257

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: CTU1
Protein: p.Pro19Leu
Coding: c.56C>T
MANE Select: NM_145232
dbSNP: rs562481846
Type: single nucleotide variant
Location: chr19:51104514 (GRCh38)
Gene constraint: LOEUF 1.978 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 84.51

Full CTU1 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Similar variants

CTU1 p.Pro19Arg Uncertain significance ★ ⚠ same residue
CTU1 p.Ala131Gly Uncertain significance ★ ⚠ same type
CTU1 p.Ala131Ser Uncertain significance ★ ⚠ same type
CTU1 p.Ala131Val Uncertain significance ★ ⚠ same type
CTU1 p.Ala154Gly Uncertain significance ★ ⚠ same type
CTU1 p.Ala154Pro Uncertain significance ★ ⚠ same type
CTU1 p.Ala206Thr Uncertain significance ★ ⚠ same type
CTU1 p.Ala240Thr 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/ctu1-p-pro19leu (accessed [today's date]).

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