Is CTSH p.Asn66= (c.198C>T) pathogenic?

CTSH p.Asn66= (c.198C>T) is classified Likely benign in CTSH (ClinVar, No assertion criteria, 1 submitter; last evaluated 2023-02-14). Rare (popmax 0.225%, afr); Associated with CTSH-related disorder.

What condition is associated with CTSH p.Asn66= (c.198C>T)?

CTSH p.Asn66= (c.198C>T) is associated with CTSH-related disorder (ClinVar).

How common is CTSH p.Asn66= (c.198C>T) in the general population?

CTSH p.Asn66= (c.198C>T) is rare (popmax 0.225%, afr) (gnomAD).

CTSH p.Asn66=

c.198C>T · rs144057694 · VCV3051073

Likely benign No assertion criteria

Classification

Likely benign

ClinVar

Review

No assertion criteria ☆☆☆☆

ClinVar · 1 submitter

gnomAD v4.1

Rare

rare (popmax 0.225%, afr)

Conditions

CTSH-related disorder

Computational evidence

Protein change
Missense predictors do not apply to this variant type; conservation carries the signal.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP -8.8	GERP -4.9
Overall
CADD	0.057	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.225% African / African-American · 169/75,010 alleles

Filtering AF 0.198% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.187%

Overall 0.012% 194/1,613,914 alleles · rare

Ancestry group	Frequency	1 in
African / African-Americangrpmax	0.225%	444
Middle Eastern	0.0166%	6,032
Admixed American	0.0133%	7,503
Remaining individualsnot grpmax-eligible	0.0112%	8,929
Finnishnot grpmax-eligible	0.00313%	31,993
South Asian	0.0022%	45,537
European (non-Finnish)	0.000424%	235,981

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: CTSH
Protein: p.Asn66=
Coding: c.198C>T
MANE Select: NM_004390
dbSNP: rs144057694
Type: single nucleotide variant
Location: chr15:78937349 (GRCh38)
Gene constraint: LOEUF 1.267 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 94.30 · 2 PDB
Residue 66: an α-helix

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

Disease context

CTSH-related disorder

Similar variants

CTSH p.Arg317Cys Likely benign same condition
CTSH p.Ala23Thr Benign ★★ same type
CTSH p.Gly11= Benign ★★ same type
CTSH p.Thr48= Benign ★★ same type
CTSH p.Ala10Val Uncertain significance ★ ⚠ same type
CTSH p.Ala149Ser Uncertain significance ★ ⚠ same type
CTSH p.Ala155Thr Uncertain significance ★ ⚠ same type
CTSH p.Ala165Val 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/ctsh-p-asn66 (accessed [today's date]).

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