Is CTSC p.Ala253Thr (c.757G>A) pathogenic?

CTSC p.Ala253Thr (c.757G>A) is classified Pathogenic in CTSC (ClinVar, Single submitter, 1 submitter; last evaluated 2025-08-21). AlphaMissense: likely benign (0.0986); Absent from gnomAD v4.1; Associated with periodontitis, aggressive.

What condition is associated with CTSC p.Ala253Thr (c.757G>A)?

CTSC p.Ala253Thr (c.757G>A) is associated with periodontitis, aggressive, Papillon-Lefevre disease, Haim-Munk syndrome (ClinVar).

How common is CTSC p.Ala253Thr (c.757G>A) in the general population?

CTSC p.Ala253Thr (c.757G>A) is absent from gnomAD v4.1 (gnomAD).

What do computational predictors say about CTSC p.Ala253Thr (c.757G>A)?

AlphaMissense predicts likely benign (score 0.0986) — an in-silico prediction, not a clinical call.

CTSC p.Ala253Thr

c.757G>A · rs968172696 · VCV2137218

Pathogenic Single submitter

Classification

Pathogenic

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.0986 · ACMG-weighted

gnomAD v4.1

Not reported

no allele count reported in gnomAD v4.1 (AN 1,583,348)

Missense predictors

0/2 damaging

AlphaMissense, SaProt · REVEL no call

Conditions

periodontitis, aggressive

Computational evidence

Protein change
AlphaMissense	0.0986	likely benign ⚠ discordant with ClinVar
REVEL	0.599	indeterminate
SaProt	LLR -9.01	tolerated
⇒ AlphaMissense and SaProt both call this tolerated; REVEL makes no call.
Splicing
SpliceAI	Δ0.87	donor loss · deltas
Pangolin	Δ0.63	loss · gain 0.49 · agrees with SpliceAI · independent
Constraint at this position
Conservation	phyloP 7.7	GERP 1.4, phastCons 1
Regional constraint	o/e 1.05	unconstrained · MANE · 44 kb · p 0.26 · regional, not allelic
Overall
CADD	34.0	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

No allele count reported in gnomAD v4.1 (AN 1,583,348). This is missing data, not an absence: the variant may or may not be present in gnomAD. Rarity (ACMG PM2) and BA1/BS1 cannot be assessed for it.

Variant & gene context

Gene: CTSC
Protein: p.Ala253Thr
Coding: c.757G>A
MANE Select: NM_001814
dbSNP: rs968172696
Type: single nucleotide variant
Location: chr11:88300530 (GRCh38)
Gene constraint: LOEUF 1.051 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 90.64 · 18 PDB

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

Disease context

periodontitis, aggressive — disease report on Sugi Atlas → Associated genes, phenotypes, clinical trials & treatments

Also linked: Papillon-Lefevre disease Haim-Munk syndrome

Similar variants

CTSC c.319-1G>A Pathogenic ★★ same condition
CTSC c.757+1G>T Likely pathogenic ★★ same condition
CTSC c.-55C>A Pathogenic ★★ same condition
CTSC p.Arg210Ter Pathogenic ★★ same condition
CTSC p.Arg250Ter Pathogenic/Likely pathogenic ★★ same condition
CTSC p.Arg272His Pathogenic/Likely pathogenic ★★ ⚠ same condition
CTSC p.Arg272Pro Pathogenic/Likely pathogenic ★★ same condition
CTSC p.Arg339Cys Pathogenic/Likely pathogenic ★★ ⚠ 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-ala253thr (accessed [today's date]).

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