Is CTU2 p.Pro430Leu (c.1289C>T) pathogenic?

CTU2 p.Pro430Leu (c.1289C>T) is classified Benign in CTU2 (ClinVar, Multiple submitters, 2 submitters; last evaluated 2026-01-14). AlphaMissense: likely benign (0.0684); Low-frequency (popmax 2.33%, afr).

How common is CTU2 p.Pro430Leu (c.1289C>T) in the general population?

CTU2 p.Pro430Leu (c.1289C>T) is low-frequency (popmax 2.33%, afr) (gnomAD).

What do computational predictors say about CTU2 p.Pro430Leu (c.1289C>T)?

AlphaMissense predicts likely benign (score 0.0684) — an in-silico prediction, not a clinical call.

CTU2 p.Pro430Leu

c.1289C>T · rs61744519 · VCV718645

Benign Multiple submitters

Classification

Benign

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 2 submitters

AlphaMissense

likely benign

0.0684 · ACMG-weighted

gnomAD v4.1

Rare

low-frequency (popmax 2.33%, afr)

Missense predictors

0/3 damaging

AlphaMissense, REVEL, SaProt

Computational evidence

Protein change
AlphaMissense	0.0684	likely benign
REVEL	0.025	moderately benign-leaning
SaProt	LLR -7.25	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 -2.1
Regional constraint	o/e 1.61	unconstrained · MANE · 8,717 bp · p 1.9e-57 · regional, not allelic
Overall
CADD	4.431	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 2.33% African / African-American · 1,750/75,010 alleles

Filtering AF 2.24% ClinGen BA1/BS1 input FAF95, joint · FAF99 2.21%

Overall 0.194% 3,126/1,612,312 alleles · low-frequency

Ancestry group	Frequency	1 in
African / African-Americangrpmax	2.33%	43
Ashkenazi Jewishnot grpmax-eligible	1.78%	56
Remaining individualsnot grpmax-eligible	0.403%	248
Middle Eastern	0.38%	263
Admixed American	0.305%	328
European (non-Finnish)	0.0323%	3,096
South Asian	0.00769%	13,009
East Asian	0.00669%	14,951

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: CTU2
Protein: p.Pro430Leu
Coding: c.1289C>T
MANE Select: NM_001012759
dbSNP: rs61744519
Type: single nucleotide variant
Location: chr16:88714674 (GRCh38)
Gene constraint: LOEUF 1.535 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 80.27

Full CTU2 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Similar variants

CTU2 c.1420-1G>A Likely pathogenic ★★ same type
CTU2 c.282+5G>A Pathogenic ★★ same type
CTU2 p.Gln243Ter Pathogenic/Likely pathogenic ★★ same type
CTU2 p.Thr291= Pathogenic ★★ same type
CTU2 p.Ala176Val Uncertain significance ★★ ⚠ same type
CTU2 p.Ala400Thr Uncertain significance ★★ ⚠ same type
CTU2 p.Arg270Cys Uncertain significance ★★ ⚠ same type
CTU2 p.Arg443Cys 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/ctu2-p-pro430leu (accessed [today's date]).

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