Is CTU2 p.Ile40Lys (c.119T>A) pathogenic?

CTU2 p.Ile40Lys (c.119T>A) is classified Uncertain significance in CTU2 (ClinVar, Single submitter, 2 submitters; last evaluated 2022-07-26). AlphaMissense: likely pathogenic (0.9556); Rare (popmax 0.116%, mid).

How common is CTU2 p.Ile40Lys (c.119T>A) in the general population?

CTU2 p.Ile40Lys (c.119T>A) is rare (popmax 0.116%, mid) (gnomAD).

What do computational predictors say about CTU2 p.Ile40Lys (c.119T>A)?

AlphaMissense predicts likely pathogenic (score 0.9556) — an in-silico prediction, not a clinical call.

CTU2 p.Ile40Lys

c.119T>A · rs61730430 · VCV2063448

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 2 submitters

AlphaMissense

likely pathogenic

0.9556 · ACMG-weighted

gnomAD v4.1

Rare

rare (popmax 0.116%, mid)

Missense predictors

2/2 damaging

AlphaMissense, SaProt · REVEL no call

Computational evidence

Protein change
AlphaMissense	0.9556	likely pathogenic · top 4% in CTU2
REVEL	0.418	indeterminate
SaProt	LLR -13.26	damaging
⇒ AlphaMissense and SaProt both call this damaging; REVEL makes no call.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 7.6	GERP 1.8, phastCons 1
Regional constraint	o/e 1.61	unconstrained · MANE · 8,717 bp · p 1.9e-57 · regional, not allelic
Overall
CADD	28.2	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 0.116% Middle Eastern · 7/6,060 alleles

Filtering AF 0.0542% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.0384%

Overall 0.0149% 241/1,613,924 alleles · rare

Ancestry group	Frequency	1 in
Middle Easterngrpmax	0.116%	866
Ashkenazi Jewishnot grpmax-eligible	0.0405%	2,467
South Asian	0.0329%	3,036
Remaining individualsnot grpmax-eligible	0.024%	4,166
European (non-Finnish)	0.0142%	7,024
Admixed American	0.00666%	15,006
Finnishnot grpmax-eligible	0.0047%	21,276
African / African-American	0.00266%	37,528

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.Ile40Lys
Coding: c.119T>A
MANE Select: NM_001012759
dbSNP: rs61730430
Type: single nucleotide variant
Location: chr16:88707186 (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-ile40lys (accessed [today's date]).

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