Is CTU2 p.Ala78Val (c.233C>T) pathogenic?

CTU2 p.Ala78Val (c.233C>T) is classified Uncertain significance in CTU2 (ClinVar, Single submitter, 1 submitter; last evaluated 2023-08-08). AlphaMissense: ambiguous (0.3622); Very rare (popmax 0.00133%, afr).

How common is CTU2 p.Ala78Val (c.233C>T) in the general population?

CTU2 p.Ala78Val (c.233C>T) is very rare (popmax 0.00133%, afr) (gnomAD).

What do computational predictors say about CTU2 p.Ala78Val (c.233C>T)?

AlphaMissense predicts ambiguous (score 0.3622) — an in-silico prediction, not a clinical call.

CTU2 p.Ala78Val

c.233C>T · rs778284872 · VCV2617442

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

ambiguous

0.3622 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 0.00133%, afr)

Computational evidence

Protein change
AlphaMissense	0.3622	ambiguous
REVEL	0.331	indeterminate
SaProt	LLR -8.95	tolerated
Splicing
SpliceAI	<0.2	all four deltas below 0.2 · C>G here scores Δ0.40 · evaluated, not missing
Constraint at this position
Conservation	phyloP 7.5	GERP 2, phastCons 1
Regional constraint	o/e 1.61	unconstrained · MANE · 8,717 bp · p 1.9e-57 · regional, not allelic
Overall
CADD	32.0	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 0.00133% African / African-American · 1/74,928 alleles

Filtering AF 0.000542% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.000428%

Overall 0.000867% 14/1,613,936 alleles · very rare

Ancestry group	Frequency	1 in
African / African-Americangrpmax	0.00133%	74,928
South Asian	0.0011%	91,084
European (non-Finnish)	0.00102%	98,333

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.Ala78Val
Coding: c.233C>T
MANE Select: NM_001012759
dbSNP: rs778284872
Type: single nucleotide variant
Location: chr16:88710233 (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-ala78val (accessed [today's date]).

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