Is CTDSP1 p.Arg48Trp (c.142C>T) pathogenic?

CTDSP1 p.Arg48Trp (c.142C>T) is classified Uncertain significance in CTDSP1 (ClinVar, Single submitter, 1 submitter; last evaluated 2025-10-03). AlphaMissense: likely benign (0.144); Very rare (popmax 0.00835%, amr).

How common is CTDSP1 p.Arg48Trp (c.142C>T) in the general population?

CTDSP1 p.Arg48Trp (c.142C>T) is very rare (popmax 0.00835%, amr) (gnomAD).

What do computational predictors say about CTDSP1 p.Arg48Trp (c.142C>T)?

AlphaMissense predicts likely benign (score 0.144) — an in-silico prediction, not a clinical call.

CTDSP1 p.Arg48Trp

c.142C>T · VCV4657453

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.144 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 0.00835%, amr)

Missense predictors

0/3 damaging

AlphaMissense, REVEL, SaProt

Computational evidence

Protein change
AlphaMissense	0.144	likely benign
REVEL	0.134	moderately benign-leaning
SaProt	LLR -9.13	tolerated
⇒ AlphaMissense, REVEL and SaProt all call this tolerated.
Splicing
SpliceAI	<0.2	all four deltas below 0.2 · C>A here scores Δ0.93 · evaluated, not missing
Constraint at this position
Conservation	phyloP 4.8	GERP -0.4, phastCons 1
Regional constraint	o/e 1.31	unconstrained · MANE · 2,070 bp · p 0.0011 · regional, not allelic
Overall
CADD	29.3	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

Grpmax group 0.00835% Admixed American · 5/59,860 alleles

Filtering AF 0.00324% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.00207%

Overall 0.000868% 14/1,613,160 alleles · very rare

Ancestry group	Frequency	1 in
Admixed Americangrpmax	0.00835%	11,972
East Asian	0.00223%	44,876
European (non-Finnish)	0.000678%	147,448

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: CTDSP1
Protein: p.Arg48Trp
Coding: c.142C>T
MANE Select: NM_021198
Type: single nucleotide variant
Location: chr2:218401638 (GRCh38)
Gene constraint: LOEUF 0.686 · pLI 0.09 (gnomAD)
Structure: AlphaFold pLDDT 82.13 · 11 PDB

Full CTDSP1 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Similar variants

CTDSP1 p.Arg48Gly Uncertain significance ★ ⚠ same residue
CTDSP1 p.Ala56Thr Benign ★★ ⚠ same type
CTDSP1 p.Ala15Thr Uncertain significance ★ ⚠ same type
CTDSP1 p.Ala15Val Uncertain significance ★ ⚠ same type
CTDSP1 p.Ala163Val Uncertain significance ★ ⚠ same type
CTDSP1 p.Ala171Val Uncertain significance ★ ⚠ same type
CTDSP1 p.Ala174Ser Uncertain significance ★ ⚠ same type
CTDSP1 p.Ala56Val 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/ctdsp1-p-arg48trp (accessed [today's date]).

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