Is CTU2 p.Val152= (c.456G>C) pathogenic?

CTU2 p.Val152= (c.456G>C) is classified Benign in CTU2 (ClinVar, Multiple submitters, 2 submitters; last evaluated 2026-02-01). Common (popmax 16.7%, amr) — too common for a highly-penetrant pathogenic allele.

CTU2 p.Val152=

Q: How common is CTU2 p.Val152= (c.456G>C) in the general population?

CTU2 p.Val152= (c.456G>C) is common (popmax 16.7%, amr) — too common for a highly-penetrant pathogenic allele (gnomAD).

c.456G>C · rs2290896 · VCV1600539

Benign Multiple submitters

Classification

Benign

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 2 submitters

gnomAD v4.1

Common

common (popmax 16.7%, amr) — too common for a highly-penetrant pathogenic allele

Computational evidence

Protein change
Missense predictors do not apply to this variant type; conservation carries the signal.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 1	GERP -0.26, phastCons 1
Overall
CADD	4.104	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 16.7% Admixed American · 9,977/59,830 alleles

Filtering AF 16.4% ClinGen BA1/BS1 input FAF95, joint · FAF99 16.3%

Overall 13.1% 210,243/1,609,376 alleles · common

Ancestry group	Frequency	1 in
Amishnot grpmax-eligible	27.7%	4
Admixed Americangrpmax	16.7%	6
East Asian	16.2%	6
Finnishnot grpmax-eligible	15.4%	7
Middle Eastern	14.8%	7
European (non-Finnish)	13.6%	7
Remaining individualsnot grpmax-eligible	13%	8
Ashkenazi Jewishnot grpmax-eligible	11.5%	9
South Asian	7.3%	14
African / African-American	5.09%	20

Amish 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: CTU2
Protein: p.Val152=
Coding: c.456G>C
MANE Select: NM_001012759
dbSNP: rs2290896
Type: single nucleotide variant
Location: chr16:88712624 (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-val152 (accessed [today's date]).

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