Is CTSW p.Arg273Gln (c.818G>A) pathogenic?

CTSW p.Arg273Gln (c.818G>A) is classified Likely benign in CTSW (ClinVar, Single submitter, 1 submitter; last evaluated 2021-06-23). AlphaMissense: likely benign (0.0821); Ultra-rare (popmax 0.0624%, eas).

How common is CTSW p.Arg273Gln (c.818G>A) in the general population?

CTSW p.Arg273Gln (c.818G>A) is ultra-rare (popmax 0.0624%, eas) (gnomAD).

What do computational predictors say about CTSW p.Arg273Gln (c.818G>A)?

AlphaMissense predicts likely benign (score 0.0821) — an in-silico prediction, not a clinical call.

CTSW p.Arg273Gln

c.818G>A · rs572206716 · VCV3078808

Likely benign Single submitter

Classification

Likely benign

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.0821 · ACMG-weighted

gnomAD v4.1

Rare

ultra-rare (popmax 0.0624%, eas)

Missense predictors

0/3 damaging

AlphaMissense, REVEL, SaProt

Computational evidence

Protein change
AlphaMissense	0.0821	likely benign
REVEL	0.004	strongly benign-leaning
SaProt	LLR -7.03	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 -2.2	GERP -2.8
Regional constraint	o/e 0.99	unconstrained · MANE · 3,760 bp · p 0.82 · regional, not allelic
Overall
CADD	0.1	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 0.0624% East Asian · 28/44,856 alleles

Filtering AF 0.0443% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.0382%

Overall 0.00372% 60/1,613,452 alleles · ultra-rare

Ancestry group	Frequency	1 in
East Asiangrpmax	0.0624%	1,602
Middle Eastern	0.0165%	6,058
South Asian	0.00439%	22,765
Remaining individualsnot grpmax-eligible	0.0032%	31,245
African / African-American	0.00267%	37,463
European (non-Finnish)	0.00186%	53,626
Admixed American	0.00167%	59,988

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: CTSW
Protein: p.Arg273Gln
Coding: c.818G>A
MANE Select: NM_001335
dbSNP: rs572206716
Type: single nucleotide variant
Location: chr11:65883222 (GRCh38)
Gene constraint: LOEUF 1.135 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 84.28

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

Similar variants

CTSW p.Ala109Gly Uncertain significance ★ ⚠ same type
CTSW p.Ala140Thr Uncertain significance ★ ⚠ same type
CTSW p.Ala28Val Uncertain significance ★ ⚠ same type
CTSW p.Ala41Asp Uncertain significance ★ ⚠ same type
CTSW p.Ala41Thr Uncertain significance ★ ⚠ same type
CTSW p.Ala71Thr Uncertain significance ★ ⚠ same type
CTSW p.Arg107Lys Uncertain significance ★ ⚠ same type
CTSW p.Arg135Gln 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/ctsw-p-arg273gln (accessed [today's date]).

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