Is CTDSPL p.Arg210Cys (c.628C>T) pathogenic?

CTDSPL p.Arg210Cys (c.628C>T) is classified Uncertain significance in CTDSPL (ClinVar, Single submitter, 1 submitter; last evaluated 2025-02-08). AlphaMissense: likely benign (0.291); Very rare (popmax 0.00333%, amr).

How common is CTDSPL p.Arg210Cys (c.628C>T) in the general population?

CTDSPL p.Arg210Cys (c.628C>T) is very rare (popmax 0.00333%, amr) (gnomAD).

What do computational predictors say about CTDSPL p.Arg210Cys (c.628C>T)?

AlphaMissense predicts likely benign (score 0.291) — an in-silico prediction, not a clinical call.

CTDSPL p.Arg210Cys

c.628C>T · VCV3837119

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.291 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 0.00333%, amr)

Missense predictors

1/2 damaging

AlphaMissense, SaProt · REVEL no call

Computational evidence

Protein change
AlphaMissense	0.291	likely benign
REVEL	0.445	indeterminate
SaProt	LLR -11.73	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 7.6	GERP 2.7, phastCons 1
Regional constraint	o/e 0.60	unconstrained · MANE · 5,154 bp · p 2.7e-06 · regional, not allelic
Overall
CADD	34.0	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 0.00333% Admixed American · 2/59,990 alleles

Filtering AF 0.000553% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.000207%

Overall 0.000558% 9/1,613,976 alleles · very rare

Ancestry group	Frequency	1 in
Admixed Americangrpmax	0.00333%	29,995
African / African-American	0.00267%	37,445
European (non-Finnish)	0.000424%	236,003

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: CTDSPL
Protein: p.Arg210Cys
Coding: c.628C>T
MANE Select: NM_001008392
Type: single nucleotide variant
Location: chr3:37975817 (GRCh38)
Gene constraint: LOEUF 0.369 · pLI 1.00 (gnomAD)
Structure: AlphaFold pLDDT 78.64 · 1 PDB
Residue 210: the fcp1 homology domain; an α-helix

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

Similar variants

CTDSPL p.Ala92Thr Uncertain significance ★ ⚠ same type
CTDSPL p.Arg184His Uncertain significance ★ ⚠ same type
CTDSPL p.Arg262Gln Uncertain significance ★ ⚠ same type
CTDSPL p.Arg262Trp Uncertain significance ★ ⚠ same type
CTDSPL p.Asn12Ser Uncertain significance ★ ⚠ same type
CTDSPL p.Asn275Lys Uncertain significance ★ ⚠ same type
CTDSPL p.Asp265Asn Uncertain significance ★ ⚠ same type
CTDSPL p.Gln29His 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/ctdspl-p-arg210cys (accessed [today's date]).

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