Is CTU2 p.Thr129= (c.387C>G) pathogenic?

CTU2 p.Thr129= (c.387C>G) is classified Likely benign in CTU2 (ClinVar, No assertion criteria, 1 submitter; last evaluated 2021-10-30). Very rare (popmax 0.00267%, afr); Associated with CTU2-related disorder.

What condition is associated with CTU2 p.Thr129= (c.387C>G)?

CTU2 p.Thr129= (c.387C>G) is associated with CTU2-related disorder (ClinVar).

How common is CTU2 p.Thr129= (c.387C>G) in the general population?

CTU2 p.Thr129= (c.387C>G) is very rare (popmax 0.00267%, afr) (gnomAD).

CTU2 p.Thr129=

c.387C>G · rs745307187 · VCV3029156

Likely benign No assertion criteria

Classification

Likely benign

ClinVar

Review

No assertion criteria ☆☆☆☆

ClinVar · 1 submitter

gnomAD v4.1

Rare

very rare (popmax 0.00267%, afr)

Conditions

CTU2-related disorder

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 -3	GERP -4.3
Overall
CADD	0.607	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.00267% African / African-American · 2/74,838 alleles

Filtering AF 0.000444% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.000166%

Overall 0.000311% 5/1,609,888 alleles · very rare

Ancestry group	Frequency	1 in
Ashkenazi Jewishnot grpmax-eligible	0.00339%	29,504
African / African-Americangrpmax	0.00267%	37,419
Remaining individualsnot grpmax-eligible	0.0016%	62,320
South Asian	0.00111%	90,166

Ashkenazi Jewish 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.Thr129=
Coding: c.387C>G
MANE Select: NM_001012759
dbSNP: rs745307187
Type: single nucleotide variant
Location: chr16:88712317 (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

Disease context

CTU2-related disorder

Similar variants

CTU2 p.Thr129Ile Uncertain significance ★ ⚠ same residue
CTU2 p.Thr291= Pathogenic ★★ same condition
CTU2 p.Leu63Pro Conflicting classifications of pathogenicity ★ ⚠ same condition
CTU2 c.1097+5G>A Uncertain significance same condition
CTU2 c.1202-8G>A Likely benign same condition
CTU2 c.1353-4G>A Likely benign same condition
CTU2 c.1419+8C>T Likely benign same condition
CTU2 c.454-6C>T Likely benign same condition

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-thr129 (accessed [today's date]).

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