Is CTDSP1 p.Arg258Trp (c.772C>T) pathogenic?

CTDSP1 p.Arg258Trp (c.772C>T) is classified Uncertain significance in CTDSP1 (ClinVar, Single submitter, 1 submitter; last evaluated 2025-06-07). AlphaMissense: likely benign (0.23); Ultra-rare (popmax 0.0154%, sas).

How common is CTDSP1 p.Arg258Trp (c.772C>T) in the general population?

CTDSP1 p.Arg258Trp (c.772C>T) is ultra-rare (popmax 0.0154%, sas) (gnomAD).

What do computational predictors say about CTDSP1 p.Arg258Trp (c.772C>T)?

AlphaMissense predicts likely benign (score 0.23) — an in-silico prediction, not a clinical call.

CTDSP1 p.Arg258Trp

c.772C>T · VCV4007911

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.23 · ACMG-weighted

gnomAD v4.1

Rare

ultra-rare (popmax 0.0154%, sas)

Missense predictors

0/3 damaging

AlphaMissense, REVEL, SaProt

Computational evidence

Protein change
AlphaMissense	0.23	likely benign
REVEL	0.189	benign-leaning
SaProt	LLR -8.64	tolerated
⇒ AlphaMissense, REVEL and SaProt all call this tolerated.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 0.18	GERP -1.2, phastCons 0.001
Regional constraint	o/e 0.61	unconstrained · MANE · 2,260 bp · p 2.7e-09 · regional, not allelic
Overall
CADD	22.5	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 0.0154% South Asian · 14/91,086 alleles

Filtering AF 0.00919% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.00735%

Overall 0.00118% 19/1,614,008 alleles · ultra-rare

Ancestry group	Frequency	1 in
South Asiangrpmax	0.0154%	6,506
Remaining individualsnot grpmax-eligible	0.0016%	62,478
African / African-American	0.00133%	74,946
European (non-Finnish)	0.000254%	393,334

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.Arg258Trp
Coding: c.772C>T
MANE Select: NM_021198
Type: single nucleotide variant
Location: chr2:218404411 (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.Arg258Gln 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-arg258trp (accessed [today's date]).

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