Is CTU2 p.Arg246Gln (c.737G>A) pathogenic?

CTU2 p.Arg246Gln (c.737G>A) is classified Uncertain significance in CTU2 (ClinVar, Single submitter, 1 submitter; last evaluated 2024-11-24). AlphaMissense: likely benign (0.2009); Very rare (popmax 0.0015%, afr).

How common is CTU2 p.Arg246Gln (c.737G>A) in the general population?

CTU2 p.Arg246Gln (c.737G>A) is very rare (popmax 0.0015%, afr) (gnomAD).

What do computational predictors say about CTU2 p.Arg246Gln (c.737G>A)?

AlphaMissense predicts likely benign (score 0.2009) — an in-silico prediction, not a clinical call.

CTU2 p.Arg246Gln

c.737G>A · VCV3706762

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.2009 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 0.0015%, afr)

Missense predictors

1/2 damaging

AlphaMissense, SaProt · REVEL no call

Computational evidence

Protein change
AlphaMissense	0.2009	likely benign
REVEL	0.38	indeterminate
SaProt	LLR -11.50	damaging
⇒ SaProt calls this damaging; AlphaMissense does not; REVEL makes no call.
Splicing
SpliceAI	Δ0.28	acceptor loss, 42 bp away · masked 0 · deltas
Pangolin	Δ0.44	loss · gain 0.02 · agrees with SpliceAI · independent
Constraint at this position
Conservation	phyloP 7.7	GERP 0.75, phastCons 1
Regional constraint	o/e 1.61	unconstrained · MANE · 8,717 bp · p 1.9e-57 · regional, not allelic
Overall
CADD	35.0	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 0.0015% African / African-American · 1/66,564 alleles

Filtering AF 0.000723% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.000566%

Overall 0.00107% 16/1,489,180 alleles · very rare

Ancestry group	Frequency	1 in
Remaining individualsnot grpmax-eligible	0.00175%	57,190
African / African-Americangrpmax	0.0015%	66,564
European (non-Finnish)	0.00125%	80,237

Remaining individuals 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.Arg246Gln
Coding: c.737G>A
MANE Select: NM_001012759
Type: single nucleotide variant
Location: chr16:88712905 (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.Arg246Trp Uncertain significance ★ ⚠ same residue
CTU2 p.Arg246= Likely benign 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

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-arg246gln (accessed [today's date]).

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