Is CTSD p.Ser148Phe (c.443C>T) pathogenic?

CTSD p.Ser148Phe (c.443C>T) is classified Uncertain significance in CTSD (ClinVar, Single submitter, 1 submitter; last evaluated 2012-07-05). AlphaMissense: ambiguous (0.4255); Absent from gnomAD v4.1.

How common is CTSD p.Ser148Phe (c.443C>T) in the general population?

CTSD p.Ser148Phe (c.443C>T) is absent from gnomAD v4.1 (gnomAD).

What do computational predictors say about CTSD p.Ser148Phe (c.443C>T)?

AlphaMissense predicts ambiguous (score 0.4255) — an in-silico prediction, not a clinical call.

CTSD p.Ser148Phe

c.443C>T · rs796052402 · VCV205352

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

ambiguous

0.4255 · ACMG-weighted

gnomAD v4.1

Absent

absent from gnomAD v4.1

Missense predictors

2/2 damaging

REVEL, SaProt · AlphaMissense no call

Computational evidence

Protein change
AlphaMissense	0.4255	ambiguous
REVEL	0.776	moderately pathogenic-leaning
SaProt	LLR -15.43	damaging
⇒ REVEL and SaProt both call this damaging; AlphaMissense makes no call.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 9.5	GERP 0.25, phastCons 1
Regional constraint	o/e 0.87	unconstrained · MANE · 10 kb · p 0.0029 · regional, not allelic
Overall
CADD	31.0	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

Absent from gnomAD v4.1. Not observed in any sequenced alleles — a rarity signal (ACMG PM2-supporting), not evidence of pathogenicity on its own.

Variant & gene context

Gene: CTSD
Protein: p.Ser148Phe
Coding: c.443C>T
MANE Select: NM_001909
dbSNP: rs796052402
Type: single nucleotide variant
Location: chr11:1758997 (GRCh38)
Gene constraint: LOEUF 0.886 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 85.69 · 9 PDB
Residue 148: a disulfide bond; a β-strand; the peptidase a1 domain

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

Similar variants

CTSD p.Ser148= Likely benign ★ same residue
CTSD c.228+1G>A Likely pathogenic ★★ same type
CTSD p.Glu82Ter Pathogenic/Likely pathogenic ★★ same type
CTSD c.828-3C>A Uncertain significance ★★ same type
CTSD c.*210C>G Uncertain significance ★★ same type
CTSD p.Ala10Ser Uncertain significance ★★ ⚠ same type
CTSD p.Ala116Thr Uncertain significance ★★ ⚠ same type
CTSD p.Ala18Pro 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/ctsd-p-ser148phe (accessed [today's date]).

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