Is CTSV p.Arg107His (c.320G>A) pathogenic?

CTSV p.Arg107His (c.320G>A) is classified Uncertain significance in CTSV (ClinVar, Single submitter, 1 submitter; last evaluated 2025-08-20). AlphaMissense: likely benign (0.1091); Rare (popmax 0.119%, sas).

How common is CTSV p.Arg107His (c.320G>A) in the general population?

CTSV p.Arg107His (c.320G>A) is rare (popmax 0.119%, sas) (gnomAD).

What do computational predictors say about CTSV p.Arg107His (c.320G>A)?

AlphaMissense predicts likely benign (score 0.1091) — an in-silico prediction, not a clinical call.

CTSV p.Arg107His

c.320G>A · VCV4235902

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.1091 · ACMG-weighted

gnomAD v4.1

Rare

rare (popmax 0.119%, sas)

Missense predictors

0/3 damaging

AlphaMissense, REVEL, SaProt

Computational evidence

Protein change
AlphaMissense	0.1091	likely benign
REVEL	0.021	moderately benign-leaning
SaProt	LLR -7.79	tolerated
⇒ AlphaMissense, REVEL and SaProt all call this tolerated.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP -8.9	GERP -3.7
Regional constraint	o/e 0.99	unconstrained · MANE · 5,091 bp · p 0.8 · regional, not allelic
Overall
CADD	3.835	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 0.119% South Asian · 108/91,072 alleles

Filtering AF 0.1% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.0936%

Overall 0.00904% 146/1,614,156 alleles · rare

Ancestry group	Frequency	1 in
South Asiangrpmax	0.119%	843
Middle Eastern	0.0165%	6,062
Remaining individualsnot grpmax-eligible	0.0096%	10,418
Admixed American	0.00666%	15,006
African / African-American	0.00533%	18,759
European (non-Finnish)	0.00195%	51,305

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.Arg107His
Coding: c.320G>A
MANE Select: NM_001333
Type: single nucleotide variant
Location: chr9:97037328 (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.Arg107Ser 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.Ala241Ser Uncertain significance ★ ⚠ same type
CTSV p.Ala241Thr Uncertain significance ★ ⚠ same type
CTSV p.Ala79Val 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-arg107his (accessed [today's date]).

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