Is CTSD p.Leu11Phe (c.31C>T) pathogenic?

CTSD p.Leu11Phe (c.31C>T) is classified Uncertain significance in CTSD (ClinVar, Single submitter, 1 submitter; last evaluated 2017-10-04). AlphaMissense: likely benign (0.0749); Very rare (popmax 0.000175%, nfe); Associated with Inborn genetic diseases.

What condition is associated with CTSD p.Leu11Phe (c.31C>T)?

CTSD p.Leu11Phe (c.31C>T) is associated with Inborn genetic diseases (ClinVar).

How common is CTSD p.Leu11Phe (c.31C>T) in the general population?

CTSD p.Leu11Phe (c.31C>T) is very rare (popmax 0.000175%, nfe) (gnomAD).

What do computational predictors say about CTSD p.Leu11Phe (c.31C>T)?

AlphaMissense predicts likely benign (score 0.0749) — an in-silico prediction, not a clinical call.

CTSD p.Leu11Phe

c.31C>T · rs2493834548 · VCV1728786

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.0749 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 0.000175%, nfe)

Missense predictors

1/3 damaging

AlphaMissense, REVEL, SaProt

Conditions

Inborn genetic diseases

Computational evidence

Protein change
AlphaMissense	0.0749	likely benign
REVEL	0.13	moderately benign-leaning
SaProt	LLR -10.13	damaging
⇒ SaProt calls this damaging; AlphaMissense and REVEL do not.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 0.84	GERP -1.7, phastCons 0.36
Regional constraint	o/e 0.87	unconstrained · MANE · 10 kb · p 0.0029 · regional, not allelic
Overall
CADD	15.03	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 0.000175% European (non-Finnish) · 2/1,143,302 alleles

Filtering AF 2.9e-05% ClinGen BA1/BS1 input FAF95, joint · FAF99 1.1e-05%

Overall 0.000145% 2/1,376,254 alleles · very rare

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: CTSD
Protein: p.Leu11Phe
Coding: c.31C>T
MANE Select: NM_001909
dbSNP: rs2493834548
Type: single nucleotide variant
Location: chr11:1763829 (GRCh38)
Gene constraint: LOEUF 0.886 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 85.69 · 9 PDB

Full CTSD 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

CTSD p.Leu11fs Pathogenic ★★ same residue
CTSD p.Ala116Thr Uncertain significance ★★ ⚠ same condition
CTSD p.Ala18Pro Uncertain significance ★★ ⚠ same condition
CTSD p.Arg205His Uncertain significance ★★ ⚠ same condition
CTSD p.Arg392His Uncertain significance ★★ ⚠ same condition
CTSD p.Asp387Asn Uncertain significance ★★ ⚠ same condition
CTSD p.Gly362Arg Uncertain significance ★★ ⚠ same condition
CTSD p.Gly391Ser 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/ctsd-p-leu11phe (accessed [today's date]).

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