Is CTU2 p.Thr291= (c.873G>A) pathogenic?

CTU2 p.Thr291= (c.873G>A) is classified Pathogenic in CTU2 (ClinVar, Multiple submitters, 8 submitters; last evaluated 2024-10-04). Ultra-rare (popmax 0.034%, mid); Associated with CTU2-related disorder.

What condition is associated with CTU2 p.Thr291= (c.873G>A)?

CTU2 p.Thr291= (c.873G>A) is associated with CTU2-related disorder, microcephaly, microcephaly, facial dysmorphism, renal agenesis, and ambiguous genitalia syndrome (ClinVar).

How common is CTU2 p.Thr291= (c.873G>A) in the general population?

CTU2 p.Thr291= (c.873G>A) is ultra-rare (popmax 0.034%, mid) (gnomAD).

CTU2 p.Thr291=

c.873G>A · rs769481947 · VCV585016

Pathogenic Multiple submitters

Classification

Pathogenic

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 8 submitters

gnomAD v4.1

Rare

ultra-rare (popmax 0.034%, mid)

Conditions

CTU2-related disorder

Computational evidence

Protein change
Missense predictors do not apply to this variant type; conservation/SpliceAI carries the signal.
Splicing
SpliceAI	Δ0.81	donor loss · deltas
Pangolin	Δ0.70	loss · gain 0.02 · agrees with SpliceAI · independent
Constraint at this position
Conservation	phyloP 4.2	GERP -0.06, phastCons 1
Overall
CADD	20.3	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.034% Middle Eastern · 2/5,882 alleles

Filtering AF 0.00598% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.00248%

Overall 0.00102% 16/1,575,520 alleles · ultra-rare exomes 16/1,423,670 · genomes 0/151,850 · joint denominator

Ancestry group	Frequency	1 in
Middle Easterngrpmax	0.034%	2,941
Remaining individualsnot grpmax-eligible	0.00329%	30,364
African / African-American	0.00137%	73,038
European (non-Finnish)	0.000942%	106,146

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.Thr291=
Coding: c.873G>A
MANE Select: NM_001012759
dbSNP: rs769481947
Type: single nucleotide variant
Location: chr16:88713447 (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

Also linked: microcephaly microcephaly, facial dysmorphism, renal agenesis, and ambiguous genitalia syndrome

Similar variants

CTU2 p.Thr291Met Uncertain significance ★ ⚠ same residue
CTU2 c.1420-1G>A Likely pathogenic ★★ same condition
CTU2 c.282+5G>A Pathogenic ★★ same condition
CTU2 p.Gln243Ter Pathogenic/Likely pathogenic ★★ same condition
CTU2 p.Gln416Ter Uncertain significance ★★ same condition
CTU2 c.1006-26A>G Benign ★★ same condition
CTU2 c.1201+29C>G Benign ★★ same condition
CTU2 c.1420-37A>G 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-thr291 (accessed [today's date]).

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