Is CTSS p.Arg113Gln (c.338G>A) pathogenic?

CTSS p.Arg113Gln (c.338G>A) is classified Likely benign in CTSS (ClinVar, Single submitter, 1 submitter; last evaluated 2023-07-25). AlphaMissense: likely benign (0.0759); Rare (popmax 0.114%, eas).

How common is CTSS p.Arg113Gln (c.338G>A) in the general population?

CTSS p.Arg113Gln (c.338G>A) is rare (popmax 0.114%, eas) (gnomAD).

What do computational predictors say about CTSS p.Arg113Gln (c.338G>A)?

AlphaMissense predicts likely benign (score 0.0759) — an in-silico prediction, not a clinical call.

CTSS p.Arg113Gln

c.338G>A · rs140031053 · VCV2613528

Likely benign Single submitter

Classification

Likely benign

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.0759 · ACMG-weighted

gnomAD v4.1

Rare

rare (popmax 0.114%, eas)

Missense predictors

0/3 damaging

AlphaMissense, REVEL, SaProt

Computational evidence

Protein change
AlphaMissense	0.0759	likely benign
REVEL	0.035	moderately benign-leaning
SaProt	LLR -4.73	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 0.95	GERP -3.1, phastCons 1
Regional constraint	o/e 0.63	unconstrained · MANE · 32 kb · p 1.1e-13 · regional, not allelic
Overall
CADD	8.899	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 0.114% East Asian · 51/44,880 alleles

Filtering AF 0.0887% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.0799%

Overall 0.00384% 62/1,614,030 alleles · rare

Ancestry group	Frequency	1 in
East Asiangrpmax	0.114%	880
Ashkenazi Jewishnot grpmax-eligible	0.00338%	29,596
African / African-American	0.00267%	37,508
Admixed American	0.00167%	60,008
European (non-Finnish)	0.000593%	168,566

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: CTSS
Protein: p.Arg113Gln
Coding: c.338G>A
MANE Select: NM_004079
dbSNP: rs140031053
Type: single nucleotide variant
Location: chr1:150755062 (GRCh38)
Gene constraint: LOEUF 0.664 · pLI 0.19 (gnomAD)
Structure: AlphaFold pLDDT 94.51 · 62 PDB
Residue 113: a UniProt-annotated variant site (in)

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

Similar variants

CTSS p.Val296= Benign ★★ same type
CTSS p.Ala243Thr Uncertain significance ★ ⚠ same type
CTSS p.Asp120Ala Uncertain significance ★ ⚠ same type
CTSS p.Asp74Asn Uncertain significance ★ ⚠ same type
CTSS p.Gly176Val Uncertain significance ★ ⚠ same type
CTSS p.His27Gln Uncertain significance ★ ⚠ same type
CTSS p.Ile193Thr Uncertain significance ★ ⚠ same type
CTSS p.Lys178Asn 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/ctss-p-arg113gln (accessed [today's date]).

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