Is CTDSP2 p.Ile7Val (c.19A>G) pathogenic?

CTDSP2 p.Ile7Val (c.19A>G) is classified Uncertain significance in CTDSP2 (ClinVar, Single submitter, 1 submitter; last evaluated 2025-12-10). AlphaMissense: ambiguous (0.4763); Very rare (popmax 0.00612%, nfe).

How common is CTDSP2 p.Ile7Val (c.19A>G) in the general population?

CTDSP2 p.Ile7Val (c.19A>G) is very rare (popmax 0.00612%, nfe) (gnomAD).

What do computational predictors say about CTDSP2 p.Ile7Val (c.19A>G)?

AlphaMissense predicts ambiguous (score 0.4763) — an in-silico prediction, not a clinical call.

CTDSP2 p.Ile7Val

c.19A>G · VCV4657458

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

ambiguous

0.4763 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 0.00612%, nfe)

Missense predictors

0/2 damaging

REVEL, SaProt · AlphaMissense indeterminate

Computational evidence

Protein change
AlphaMissense	0.4763	ambiguous
REVEL	0.067	moderately benign-leaning
SaProt	LLR -5.70	tolerated
⇒ REVEL and SaProt both call this tolerated; AlphaMissense is indeterminate.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 5.9	GERP 1.7, phastCons 1
Regional constraint	o/e 1.04	unconstrained · MANE · 19 kb · p 0.71 · regional, not allelic
Overall
CADD	23.1	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 0.00612% European (non-Finnish) · 72/1,177,138 alleles

Filtering AF 0.00496% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.00456%

Overall 0.00473% 76/1,606,936 alleles · very rare exomes 75/1,454,806 · genomes 1/152,130 · joint denominator

Ancestry group	Frequency	1 in
European (non-Finnish)grpmax	0.00612%	16,349
Remaining individualsnot grpmax-eligible	0.00483%	20,715
East Asian	0.00224%	44,598

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: CTDSP2
Protein: p.Ile7Val
Coding: c.19A>G
MANE Select: NM_005730
Type: single nucleotide variant
Location: chr12:57846417 (GRCh38)
Gene constraint: LOEUF 0.511 · pLI 0.97 (gnomAD)
Structure: AlphaFold pLDDT 78.73 · 1 PDB

Full CTDSP2 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Similar variants

CTDSP2 p.Ala66Glu Uncertain significance ★ ⚠ same type
CTDSP2 p.Arg179Trp Uncertain significance ★ ⚠ same type
CTDSP2 p.Arg184Gln Uncertain significance ★ ⚠ same type
CTDSP2 p.Arg46Cys Uncertain significance ★ ⚠ same type
CTDSP2 p.Arg46Gly Uncertain significance ★ ⚠ same type
CTDSP2 p.Glu155Asp Uncertain significance ★ ⚠ same type
CTDSP2 p.Glu228Lys Uncertain significance ★ ⚠ same type
CTDSP2 p.Gly34Val 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/ctdsp2-p-ile7val (accessed [today's date]).

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