Is CTU2 p.Ala237Val (c.710C>T) pathogenic?

CTU2 p.Ala237Val (c.710C>T) is classified Uncertain significance in CTU2 (ClinVar, Single submitter, 1 submitter; last evaluated 2022-09-01). AlphaMissense: ambiguous (0.3516); Ultra-rare (popmax 0.0428%, mid).

How common is CTU2 p.Ala237Val (c.710C>T) in the general population?

CTU2 p.Ala237Val (c.710C>T) is ultra-rare (popmax 0.0428%, mid) (gnomAD).

What do computational predictors say about CTU2 p.Ala237Val (c.710C>T)?

AlphaMissense predicts ambiguous (score 0.3516) — an in-silico prediction, not a clinical call.

CTU2 p.Ala237Val

c.710C>T · rs200180602 · VCV1379388

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

ambiguous

0.3516 · ACMG-weighted

gnomAD v4.1

Rare

ultra-rare (popmax 0.0428%, mid)

Missense predictors

1/2 damaging

REVEL, SaProt · AlphaMissense no call

Computational evidence

Protein change
AlphaMissense	0.3516	ambiguous
REVEL	0.184	benign-leaning
SaProt	LLR -10.91	damaging
⇒ SaProt calls this damaging; REVEL does not; AlphaMissense makes no call.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 7.5	GERP 1.9, phastCons 1
Regional constraint	o/e 1.61	unconstrained · MANE · 8,717 bp · p 1.9e-57 · regional, not allelic
Overall
CADD	26.0	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 0.0428% Middle Eastern · 2/4,670 alleles

Filtering AF 0.0134% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.0128%

Overall 0.0144% 221/1,535,430 alleles · ultra-rare

Ancestry group	Frequency	1 in
Finnishnot grpmax-eligible	0.0546%	1,830
Middle Easterngrpmax	0.0428%	2,335
European (non-Finnish)	0.0153%	6,526
Remaining individualsnot grpmax-eligible	0.00848%	11,792
South Asian	0.00747%	13,392
Ashkenazi Jewishnot grpmax-eligible	0.00408%	24,502

Finnish 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.Ala237Val
Coding: c.710C>T
MANE Select: NM_001012759
dbSNP: rs200180602
Type: single nucleotide variant
Location: chr16:88712878 (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.Ala237Thr 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-ala237val (accessed [today's date]).

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