Is CTU2 p.Phe293Tyr (c.878T>A) pathogenic?

CTU2 p.Phe293Tyr (c.878T>A) is classified Uncertain significance in CTU2 (ClinVar, Single submitter, 1 submitter; last evaluated 2025-01-09). AlphaMissense: ambiguous (0.4413); Very rare (popmax 0.00831%, nfe).

How common is CTU2 p.Phe293Tyr (c.878T>A) in the general population?

CTU2 p.Phe293Tyr (c.878T>A) is very rare (popmax 0.00831%, nfe) (gnomAD).

What do computational predictors say about CTU2 p.Phe293Tyr (c.878T>A)?

AlphaMissense predicts ambiguous (score 0.4413) — an in-silico prediction, not a clinical call.

CTU2 p.Phe293Tyr

c.878T>A · rs757074584 · VCV2399532

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

ambiguous

0.4413 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 0.00831%, nfe)

Computational evidence

Protein change
AlphaMissense	0.4413	ambiguous
REVEL	0.331	indeterminate
SaProt	LLR -10.32	damaging
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 7.8	GERP 2.1, phastCons 1
Regional constraint	o/e 1.61	unconstrained · MANE · 8,717 bp · p 1.9e-57 · regional, not allelic
Overall
CADD	26.8	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 0.00831% European (non-Finnish) · 98/1,179,624 alleles

Filtering AF 0.00697% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.00641%

Overall 0.00627% 101/1,611,998 alleles · very rare

Ancestry group	Frequency	1 in
European (non-Finnish)grpmax	0.00831%	12,037
Remaining individualsnot grpmax-eligible	0.0032%	31,222
Finnishnot grpmax-eligible	0.0016%	62,596

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.Phe293Tyr
Coding: c.878T>A
MANE Select: NM_001012759
dbSNP: rs757074584
Type: single nucleotide variant
Location: chr16:88713651 (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 p.Phe293Leu Uncertain significance ★ ⚠ same residue
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

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-phe293tyr (accessed [today's date]).

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