Is CTU2 p.Ala108Pro (c.322G>C) pathogenic?

CTU2 p.Ala108Pro (c.322G>C) is classified Benign in CTU2 (ClinVar, Multiple submitters, 3 submitters; last evaluated 2026-01-14). AlphaMissense: likely benign (0.025); Common (popmax 5.71%, afr) — too common for a highly-penetrant pathogenic allele.

What do computational predictors say about CTU2 p.Ala108Pro (c.322G>C)?

AlphaMissense predicts likely benign (score 0.025) — an in-silico prediction, not a clinical call.

CTU2 p.Ala108Pro

Q: How common is CTU2 p.Ala108Pro (c.322G>C) in the general population?

CTU2 p.Ala108Pro (c.322G>C) is common (popmax 5.71%, afr) — too common for a highly-penetrant pathogenic allele (gnomAD).

c.322G>C · rs61738915 · VCV786641

Benign Multiple submitters

Classification

Benign

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 3 submitters

AlphaMissense

likely benign

0.025 · ACMG-weighted

gnomAD v4.1

Common

common (popmax 5.71%, afr) — too common for a highly-penetrant pathogenic allele

Missense predictors

0/3 damaging

AlphaMissense, REVEL, SaProt

Computational evidence

Protein change
AlphaMissense	0.025	likely benign
REVEL	0.214	benign-leaning
SaProt	LLR -0.21	tolerated
⇒ AlphaMissense, REVEL and SaProt all call this tolerated.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 5.9	GERP 0.99, phastCons 1
Regional constraint	o/e 1.61	unconstrained · MANE · 8,717 bp · p 1.9e-57 · regional, not allelic
Overall
CADD	9.654	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 5.71% African / African-American · 4,282/74,966 alleles

Filtering AF 5.57% ClinGen BA1/BS1 input FAF95, joint · FAF99 5.51%

Overall 0.303% 4,870/1,608,678 alleles · common

Ancestry group	Frequency	1 in
African / African-Americangrpmax	5.71%	18
Remaining individualsnot grpmax-eligible	0.409%	244
Admixed American	0.373%	268
Middle Eastern	0.314%	318
South Asian	0.0233%	4,289
European (non-Finnish)	0.00595%	16,811

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.Ala108Pro
Coding: c.322G>C
MANE Select: NM_001012759
dbSNP: rs61738915
Type: single nucleotide variant
Location: chr16:88711674 (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.Ala108Val 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-ala108pro (accessed [today's date]).

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