Is CTSV p.Ala241Ser (c.721G>T) pathogenic?

CTSV p.Ala241Ser (c.721G>T) is classified Uncertain significance in CTSV (ClinVar, Single submitter, 1 submitter; last evaluated 2024-02-17). AlphaMissense: likely benign (0.1591); Absent from gnomAD v4.1.

How common is CTSV p.Ala241Ser (c.721G>T) in the general population?

CTSV p.Ala241Ser (c.721G>T) is absent from gnomAD v4.1 (gnomAD).

What do computational predictors say about CTSV p.Ala241Ser (c.721G>T)?

AlphaMissense predicts likely benign (score 0.1591) — an in-silico prediction, not a clinical call.

CTSV p.Ala241Ser

c.721G>T · rs149543665 · VCV3078794

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.1591 · ACMG-weighted

gnomAD v4.1

Absent

absent from gnomAD v4.1

Missense predictors

1/3 damaging

AlphaMissense, REVEL, SaProt

Computational evidence

Protein change
AlphaMissense	0.1591	likely benign
REVEL	0.275	benign-leaning
SaProt	LLR -11.78	damaging
⇒ SaProt calls this damaging; AlphaMissense and REVEL do not.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 6	GERP 1.8, phastCons 1
Regional constraint	o/e 0.99	unconstrained · MANE · 5,091 bp · p 0.8 · regional, not allelic
Overall
CADD	22.7	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

Absent from gnomAD v4.1. Not observed in any sequenced alleles — a rarity signal (ACMG PM2-supporting), not evidence of pathogenicity on its own.

Variant & gene context

Gene: CTSV
Protein: p.Ala241Ser
Coding: c.721G>T
MANE Select: NM_001333
dbSNP: rs149543665
Type: single nucleotide variant
Location: chr9:97035594 (GRCh38)
Gene constraint: LOEUF 1.374 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 93.13 · 25 PDB
Residue 241: an α-helix

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

Similar variants

CTSV p.Ala241Thr Uncertain significance ★ ⚠ same residue
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.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-ala241ser (accessed [today's date]).

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