Is CTSV p.Val240Ala (c.719T>C) pathogenic?

CTSV p.Val240Ala (c.719T>C) is classified Uncertain significance in CTSV (ClinVar, Single submitter, 1 submitter; last evaluated 2025-09-25). AlphaMissense: ambiguous (0.3753); Very rare (popmax 0.00417%, nfe).

How common is CTSV p.Val240Ala (c.719T>C) in the general population?

CTSV p.Val240Ala (c.719T>C) is very rare (popmax 0.00417%, nfe) (gnomAD).

What do computational predictors say about CTSV p.Val240Ala (c.719T>C)?

AlphaMissense predicts ambiguous (score 0.3753) — an in-silico prediction, not a clinical call.

CTSV p.Val240Ala

c.719T>C · rs753472874 · VCV2540080

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

ambiguous

0.3753 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 0.00417%, nfe)

Computational evidence

Protein change
AlphaMissense	0.3753	ambiguous
REVEL	0.353	indeterminate
SaProt	LLR -8.89	tolerated
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 11	GERP 1.8, phastCons 1
Regional constraint	o/e 0.99	unconstrained · MANE · 5,091 bp · p 0.8 · regional, not allelic
Overall
CADD	23.8	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 0.00417% European (non-Finnish) · 49/1,175,492 alleles

Filtering AF 0.00319% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.00287%

Overall 0.00318% 51/1,605,830 alleles · very rare

Ancestry group	Frequency	1 in
European (non-Finnish)grpmax	0.00417%	23,990
African / African-American	0.00268%	37,295

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.Val240Ala
Coding: c.719T>C
MANE Select: NM_001333
dbSNP: rs753472874
Type: single nucleotide variant
Location: chr9:97035596 (GRCh38)
Gene constraint: LOEUF 1.374 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 93.13 · 25 PDB
Residue 240: an α-helix

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

Similar variants

CTSV p.Asn179= Benign ★★ same type
CTSV p.Ala15Asp Uncertain significance ★ ⚠ 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

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-val240ala (accessed [today's date]).

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