Is CTDSP1 p.Arg48Gly (c.142C>G) pathogenic?

CTDSP1 p.Arg48Gly (c.142C>G) is classified Uncertain significance in CTDSP1 (ClinVar, Single submitter, 1 submitter; last evaluated 2021-12-06). AlphaMissense: likely benign (0.0884); Very rare (popmax 0.0044%, sas).

How common is CTDSP1 p.Arg48Gly (c.142C>G) in the general population?

CTDSP1 p.Arg48Gly (c.142C>G) is very rare (popmax 0.0044%, sas) (gnomAD).

What do computational predictors say about CTDSP1 p.Arg48Gly (c.142C>G)?

AlphaMissense predicts likely benign (score 0.0884) — an in-silico prediction, not a clinical call.

CTDSP1 p.Arg48Gly

c.142C>G · rs547460809 · VCV2241804

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.0884 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 0.0044%, sas)

Missense predictors

0/3 damaging

AlphaMissense, REVEL, SaProt

Computational evidence

Protein change
AlphaMissense	0.0884	likely benign
REVEL	0.082	moderately benign-leaning
SaProt	LLR -6.79	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	24.1	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 0.0044% South Asian · 4/91,012 alleles

Filtering AF 0.00143% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.000892%

Overall 0.00031% 5/1,613,160 alleles · very rare

Ancestry group	Frequency	1 in
South Asiangrpmax	0.0044%	22,753
European (non-Finnish)	8.48e-05%	1,179,581

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.Arg48Gly
Coding: c.142C>G
MANE Select: NM_021198
dbSNP: rs547460809
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.Arg48Trp 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-arg48gly (accessed [today's date]).

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