Is CTSV p.Ala15Asp (c.44C>A) pathogenic?

CTSV p.Ala15Asp (c.44C>A) is classified Uncertain significance in CTSV (ClinVar, Single submitter, 1 submitter; last evaluated 2025-05-21). AlphaMissense: ambiguous (0.3943); Very rare (popmax 0.00178%, nfe).

How common is CTSV p.Ala15Asp (c.44C>A) in the general population?

CTSV p.Ala15Asp (c.44C>A) is very rare (popmax 0.00178%, nfe) (gnomAD).

What do computational predictors say about CTSV p.Ala15Asp (c.44C>A)?

AlphaMissense predicts ambiguous (score 0.3943) — an in-silico prediction, not a clinical call.

CTSV p.Ala15Asp

c.44C>A · VCV4008194

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

ambiguous

0.3943 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 0.00178%, nfe)

Computational evidence

Protein change
AlphaMissense	0.3943	ambiguous
REVEL	0.561	indeterminate
SaProt	LLR -13.62	damaging
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 2.1	GERP 1.4, phastCons 0.97
Regional constraint	o/e 0.99	unconstrained · MANE · 5,091 bp · p 0.8 · regional, not allelic
Overall
CADD	18.92	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 0.00178% European (non-Finnish) · 21/1,179,968 alleles

Filtering AF 0.00114% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.000971%

Overall 0.0015% 22/1,461,826 alleles · very rare

Ancestry group	Frequency	1 in
European (non-Finnish)grpmax	0.00178%	56,189
Remaining individualsnot grpmax-eligible	0.0016%	62,510

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: CTSV
Protein: p.Ala15Asp
Coding: c.44C>A
MANE Select: NM_001333
Type: single nucleotide variant
Location: chr9:97038000 (GRCh38)
Gene constraint: LOEUF 1.374 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 93.13 · 25 PDB

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

Similar variants

CTSV p.Asn179= Benign ★★ same type
CTSV p.Ala186Asp Uncertain significance ★ ⚠ same type
CTSV p.Ala186Thr Uncertain significance ★ ⚠ same type
CTSV p.Ala241Ser Uncertain significance ★ ⚠ same type
CTSV p.Ala241Thr Uncertain significance ★ ⚠ same type
CTSV p.Ala79Val Uncertain significance ★ ⚠ same type
CTSV p.Arg101Gly Uncertain significance ★ ⚠ same type
CTSV p.Arg107His 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/ctsv-p-ala15asp (accessed [today's date]).

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