Is CTDSPL2 p.Glu45Ala (c.134A>C) pathogenic?

CTDSPL2 p.Glu45Ala (c.134A>C) is classified Uncertain significance in CTDSPL2 (ClinVar, Single submitter, 1 submitter; last evaluated 2025-06-17). AlphaMissense: likely benign (0.1653); Absent from gnomAD v4.1.

How common is CTDSPL2 p.Glu45Ala (c.134A>C) in the general population?

CTDSPL2 p.Glu45Ala (c.134A>C) is absent from gnomAD v4.1 (gnomAD).

What do computational predictors say about CTDSPL2 p.Glu45Ala (c.134A>C)?

AlphaMissense predicts likely benign (score 0.1653) — an in-silico prediction, not a clinical call.

CTDSPL2 p.Glu45Ala

c.134A>C · VCV4235577

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.1653 · ACMG-weighted

gnomAD v4.1

Absent

absent from gnomAD v4.1

Missense predictors

0/2 damaging

AlphaMissense, SaProt · REVEL no call

Computational evidence

Protein change
AlphaMissense	0.1653	likely benign
REVEL	0.445	indeterminate
SaProt	LLR -6.41	tolerated
⇒ AlphaMissense and SaProt both call this tolerated; REVEL makes no call.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 11	GERP 2.8, phastCons 1
Regional constraint	o/e 0.97	unconstrained · MANE · 37 kb · p 0.6 · regional, not allelic
Overall
CADD	21.8	PHRED · no single calibrated threshold — expert panels disagree

ClinVar classifies this uncertain; the computational predictors unanimously lean tolerated — a triage signal, not a reclassification

AlphaMissense carries the ACMG weight for missense; REVEL and SaProt are independent agreement signals.

Population frequency

gnomAD v4.1 · exomes + genomes

Absent from gnomAD v4.1. Not observed in any sequenced alleles — a rarity signal (ACMG PM2-supporting), not evidence of pathogenicity on its own.

Variant & gene context

Gene: CTDSPL2
Protein: p.Glu45Ala
Coding: c.134A>C
MANE Select: NM_016396
Type: single nucleotide variant
Location: chr15:44459148 (GRCh38)
Gene constraint: LOEUF 0.184 · pLI 1.00 (gnomAD)
Structure: AlphaFold pLDDT 66.94
Residue 45: the 'disordered' region

Full CTDSPL2 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Similar variants

CTDSPL2 p.Ala244Val Benign ★★ same type
CTDSPL2 p.Pro166= Benign ★★ same type
CTDSPL2 p.Ala199Pro Uncertain significance ★ ⚠ same type
CTDSPL2 p.Ala204Gly Uncertain significance ★ ⚠ same type
CTDSPL2 p.Ala231Thr Uncertain significance ★ ⚠ same type
CTDSPL2 p.Ala8Gly Uncertain significance ★ ⚠ same type
CTDSPL2 p.Ala8Thr Uncertain significance ★ ⚠ same type
CTDSPL2 p.Arg19Cys 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/ctdspl2-p-glu45ala (accessed [today's date]).

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