Is CTU1 p.Arg161Ser (c.481C>A) pathogenic?

CTU1 p.Arg161Ser (c.481C>A) is classified Uncertain significance in CTU1 (ClinVar, Single submitter, 1 submitter; last evaluated 2025-06-18). AlphaMissense: likely benign (0.2528); Very rare (popmax 0.00296%, afr).

How common is CTU1 p.Arg161Ser (c.481C>A) in the general population?

CTU1 p.Arg161Ser (c.481C>A) is very rare (popmax 0.00296%, afr) (gnomAD).

What do computational predictors say about CTU1 p.Arg161Ser (c.481C>A)?

AlphaMissense predicts likely benign (score 0.2528) — an in-silico prediction, not a clinical call.

CTU1 p.Arg161Ser

c.481C>A · VCV4235985

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.2528 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 0.00296%, afr)

Missense predictors

1/3 damaging

AlphaMissense, REVEL, SaProt

Computational evidence

Protein change
AlphaMissense	0.2528	likely benign
REVEL	0.049	moderately benign-leaning
SaProt	LLR -10.98	damaging
⇒ SaProt calls this damaging; AlphaMissense and REVEL do not.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 9.1	GERP 1.1, phastCons 1
Regional constraint	o/e 1.09	unconstrained · MANE · 5,790 bp · p 0.053 · regional, not allelic
Overall
CADD	21.4	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 0.00296% African / African-American · 2/67,680 alleles

Filtering AF 0.00049% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.000184%

Overall 0.00131% 2/152,238 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.Arg161Ser
Coding: c.481C>A
MANE Select: NM_145232
Type: single nucleotide variant
Location: chr19:51104089 (GRCh38)
Gene constraint: LOEUF 1.978 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 84.51

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-arg161ser (accessed [today's date]).

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