Is CTSW p.Asp64His (c.190G>C) pathogenic?

CTSW p.Asp64His (c.190G>C) is classified Uncertain significance in CTSW (ClinVar, Single submitter, 1 submitter; last evaluated 2023-09-29). AlphaMissense: likely benign (0.1244); Very rare (popmax 0.00553%, nfe).

How common is CTSW p.Asp64His (c.190G>C) in the general population?

CTSW p.Asp64His (c.190G>C) is very rare (popmax 0.00553%, nfe) (gnomAD).

What do computational predictors say about CTSW p.Asp64His (c.190G>C)?

AlphaMissense predicts likely benign (score 0.1244) — an in-silico prediction, not a clinical call.

CTSW p.Asp64His

c.190G>C · rs141204630 · VCV3078799

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.1244 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 0.00553%, nfe)

Missense predictors

0/2 damaging

AlphaMissense, SaProt · REVEL no call

Computational evidence

Protein change
AlphaMissense	0.1244	likely benign
REVEL	0.317	indeterminate
SaProt	LLR -5.69	tolerated
⇒ AlphaMissense and SaProt both call this tolerated; REVEL makes no call.
Splicing
SpliceAI	<0.2	all four deltas below 0.2 · G>T here scores Δ0.25 · evaluated, not missing
Pangolin	Δ0.26	loss · gain 0.14 · SpliceAI below 0.2 · independent
Constraint at this position
Conservation	phyloP 0.94	GERP -2, phastCons 0.3
Regional constraint	o/e 0.99	unconstrained · MANE · 3,760 bp · p 0.82 · regional, not allelic
Overall
CADD	15.1	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 0.00553% European (non-Finnish) · 65/1,175,192 alleles

Filtering AF 0.00445% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.00405%

Overall 0.00424% 68/1,604,952 alleles · very rare

Ancestry group	Frequency	1 in
European (non-Finnish)grpmax	0.00553%	18,080
Remaining individualsnot grpmax-eligible	0.00483%	20,724

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.Asp64His
Coding: c.190G>C
MANE Select: NM_001335
dbSNP: rs141204630
Type: single nucleotide variant
Location: chr11:65881424 (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-asp64his (accessed [today's date]).

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