Is CTDSP1 p.Arg194Trp (c.580C>T) pathogenic?

CTDSP1 p.Arg194Trp (c.580C>T) is classified Uncertain significance in CTDSP1 (ClinVar, Single submitter, 1 submitter; last evaluated 2024-03-20). AlphaMissense: ambiguous (0.5623); Very rare (popmax 8.47e-05%, nfe).

How common is CTDSP1 p.Arg194Trp (c.580C>T) in the general population?

CTDSP1 p.Arg194Trp (c.580C>T) is very rare (popmax 8.47e-05%, nfe) (gnomAD).

What do computational predictors say about CTDSP1 p.Arg194Trp (c.580C>T)?

AlphaMissense predicts ambiguous (score 0.5623) — an in-silico prediction, not a clinical call.

CTDSP1 p.Arg194Trp

c.580C>T · VCV3270047

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

ambiguous

0.5623 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 8.47e-05%, nfe)

Computational evidence

Protein change
AlphaMissense	0.5623	ambiguous
REVEL	0.339	indeterminate
SaProt	LLR -12.78	damaging
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 0.65	GERP 0.001, phastCons 0.99
Regional constraint	o/e 0.61	unconstrained · MANE · 2,260 bp · p 2.7e-09 · regional, not allelic
Overall
CADD	25.8	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 8.47e-05% European (non-Finnish) · 1/1,179,992 alleles

Overall 0.000137% 2/1,461,732 alleles · very rare

Ancestry group	Frequency	1 in
Finnishnot grpmax-eligible	0.00156%	63,968
European (non-Finnish)grpmax	8.47e-05%	1,179,993

Finnish 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: CTDSP1
Protein: p.Arg194Trp
Coding: c.580C>T
MANE Select: NM_021198
Type: single nucleotide variant
Location: chr2:218403340 (GRCh38)
Gene constraint: LOEUF 0.686 · pLI 0.09 (gnomAD)
Structure: AlphaFold pLDDT 82.13 · 11 PDB
Residue 194: the fcp1 homology domain; an α-helix

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

Similar variants

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
CTDSP1 p.Ala5Val 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-arg194trp (accessed [today's date]).

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