Is CTSC p.Ser55Leu (c.164C>T) pathogenic?

CTSC p.Ser55Leu (c.164C>T) is classified Uncertain significance in CTSC (ClinVar, Single submitter, 1 submitter; last evaluated 2023-02-15). AlphaMissense: likely benign (0.1229); Very rare (popmax 0.00947%, afr); Associated with Inborn genetic diseases.

What condition is associated with CTSC p.Ser55Leu (c.164C>T)?

CTSC p.Ser55Leu (c.164C>T) is associated with Inborn genetic diseases (ClinVar).

How common is CTSC p.Ser55Leu (c.164C>T) in the general population?

CTSC p.Ser55Leu (c.164C>T) is very rare (popmax 0.00947%, afr) (gnomAD).

What do computational predictors say about CTSC p.Ser55Leu (c.164C>T)?

AlphaMissense predicts likely benign (score 0.1229) — an in-silico prediction, not a clinical call.

CTSC p.Ser55Leu

c.164C>T · rs377512795 · VCV2485167

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.1229 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 0.00947%, afr)

Missense predictors

2/3 damaging

AlphaMissense, REVEL, SaProt

Conditions

Inborn genetic diseases

Computational evidence

Protein change
AlphaMissense	0.1229	likely benign
REVEL	0.651	pathogenic-leaning
SaProt	LLR -10.26	damaging
⇒ REVEL and SaProt call this damaging; AlphaMissense does not.
Splicing
SpliceAI	<0.2	all four deltas below 0.2 · G>T here scores Δ0.35 · evaluated, not missing
Constraint at this position
Conservation	phyloP 7.1	GERP 1.4, phastCons 1
Regional constraint	o/e 1.05	unconstrained · MANE · 44 kb · p 0.26 · regional, not allelic
Overall
CADD	27.2	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 0.00947% African / African-American · 7/73,924 alleles

Filtering AF 0.00443% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.00312%

Overall 0.000636% 10/1,573,442 alleles · very rare

Ancestry group	Frequency	1 in
African / African-Americangrpmax	0.00947%	10,561
South Asian	0.00233%	43,002
Remaining individualsnot grpmax-eligible	0.00164%	60,868

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: CTSC
Protein: p.Ser55Leu
Coding: c.164C>T
MANE Select: NM_001814
dbSNP: rs377512795
Type: single nucleotide variant
Location: chr11:88337509 (GRCh38)
Gene constraint: LOEUF 1.051 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 90.64 · 18 PDB
Residue 55: a disulfide bond; an α-helix

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

Disease context

Inborn genetic diseases — disease report on Sugi Atlas → Associated genes, phenotypes, clinical trials & treatments

Similar variants

CTSC p.Ser55= Likely benign ★ same residue
CTSC p.Ala269Val Uncertain significance ★★ ⚠ same condition
CTSC p.Arg442His Uncertain significance ★★ ⚠ same condition
CTSC p.Ile282Val Uncertain significance ★★ ⚠ same condition
CTSC p.Phe439Leu Uncertain significance ★★ ⚠ same condition
CTSC p.Thr188Ala Uncertain significance ★★ ⚠ same condition
CTSC p.Tyr32Cys Uncertain significance ★★ ⚠ same condition
CTSC p.Val22Leu Uncertain significance ★★ ⚠ same condition

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/ctsc-p-ser55leu (accessed [today's date]).

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