Is CTU1 p.Ala341Thr (c.1021G>A) pathogenic?

CTU1 p.Ala341Thr (c.1021G>A) is classified Likely benign in CTU1 (ClinVar, Single submitter, 1 submitter; last evaluated 2024-06-04). AlphaMissense: likely benign (0.0809); Very rare (popmax 0.000292%, nfe).

How common is CTU1 p.Ala341Thr (c.1021G>A) in the general population?

CTU1 p.Ala341Thr (c.1021G>A) is very rare (popmax 0.000292%, nfe) (gnomAD).

What do computational predictors say about CTU1 p.Ala341Thr (c.1021G>A)?

AlphaMissense predicts likely benign (score 0.0809) — an in-silico prediction, not a clinical call.

CTU1 p.Ala341Thr

c.1021G>A · VCV3270263

Likely benign Single submitter

Classification

Likely benign

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.0809 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 0.000292%, nfe)

Missense predictors

0/2 damaging

AlphaMissense, SaProt

Computational evidence

Protein change
AlphaMissense	0.0809	likely benign
SaProt	LLR -7.30	tolerated
⇒ AlphaMissense and SaProt both call this tolerated.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP -2	GERP -1.6
Regional constraint	o/e 0.58	unconstrained · MANE · 174 bp · p 4.8e-05 · regional, not allelic
Overall
CADD	0.05	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 0.000292% European (non-Finnish) · 3/1,027,306 alleles

Filtering AF 7.8e-05% ClinGen BA1/BS1 input FAF95, joint · FAF99 2.2e-05%

Overall 0.000229% 3/1,307,802 alleles · very rare

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: CTU1
Protein: p.Ala341Thr
Coding: c.1021G>A
MANE Select: NM_145232
Type: single nucleotide variant
Location: chr19:51098627 (GRCh38)
Gene constraint: LOEUF 1.978 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 84.51
Residue 341: the 'disordered' region

Full CTU1 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Similar variants

CTU1 p.Ala131Gly Uncertain significance ★ ⚠ same type
CTU1 p.Ala131Ser Uncertain significance ★ ⚠ same type
CTU1 p.Ala131Val Uncertain significance ★ ⚠ same type
CTU1 p.Ala154Gly Uncertain significance ★ ⚠ same type
CTU1 p.Ala154Pro Uncertain significance ★ ⚠ same type
CTU1 p.Ala206Thr Uncertain significance ★ ⚠ same type
CTU1 p.Ala240Thr Uncertain significance ★ ⚠ same type
CTU1 p.Ala276Val 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/ctu1-p-ala341thr (accessed [today's date]).

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