Is CTDSP1 p.Ser245Cys (c.733A>T) pathogenic?

CTDSP1 p.Ser245Cys (c.733A>T) is classified Uncertain significance in CTDSP1 (ClinVar, Single submitter, 1 submitter; last evaluated 2024-01-31). AlphaMissense: likely benign (0.1446); Very rare (popmax 0.00223%, eas).

How common is CTDSP1 p.Ser245Cys (c.733A>T) in the general population?

CTDSP1 p.Ser245Cys (c.733A>T) is very rare (popmax 0.00223%, eas) (gnomAD).

What do computational predictors say about CTDSP1 p.Ser245Cys (c.733A>T)?

AlphaMissense predicts likely benign (score 0.1446) — an in-silico prediction, not a clinical call.

CTDSP1 p.Ser245Cys

c.733A>T · rs1002567339 · VCV3078600

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.1446 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 0.00223%, eas)

Missense predictors

1/2 damaging

AlphaMissense, SaProt · REVEL no call

Computational evidence

Protein change
AlphaMissense	0.1446	likely benign
REVEL	0.337	indeterminate
SaProt	LLR -11.95	damaging
⇒ SaProt calls this damaging; AlphaMissense does not; REVEL makes no call.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 11	GERP 2.2, phastCons 1
Regional constraint	o/e 0.61	unconstrained · MANE · 2,260 bp · p 2.7e-09 · regional, not allelic
Overall
CADD	28.2	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 0.00223% East Asian · 1/44,870 alleles

Overall 6.84e-05% 1/1,461,416 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: CTDSP1
Protein: p.Ser245Cys
Coding: c.733A>T
MANE Select: NM_021198
dbSNP: rs1002567339
Type: single nucleotide variant
Location: chr2:218404372 (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.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-ser245cys (accessed [today's date]).

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