Is CTSE p.Val248Phe (c.742G>T) pathogenic?

CTSE p.Val248Phe (c.742G>T) is classified Uncertain significance in CTSE (ClinVar, Single submitter, 1 submitter; last evaluated 2025-08-09). AlphaMissense: likely benign (0.3328); Rare (popmax 0.669%, afr).

How common is CTSE p.Val248Phe (c.742G>T) in the general population?

CTSE p.Val248Phe (c.742G>T) is rare (popmax 0.669%, afr) (gnomAD).

What do computational predictors say about CTSE p.Val248Phe (c.742G>T)?

AlphaMissense predicts likely benign (score 0.3328) — an in-silico prediction, not a clinical call.

CTSE p.Val248Phe

c.742G>T · VCV4235853

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.3328 · ACMG-weighted

gnomAD v4.1

Rare

rare (popmax 0.669%, afr)

Missense predictors

1/2 damaging

AlphaMissense, SaProt

Computational evidence

Protein change
AlphaMissense	0.3328	likely benign
SaProt	LLR -13.12	damaging
⇒ SaProt calls this damaging; AlphaMissense does not.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 0.94	GERP -2.8, phastCons 1
Regional constraint	o/e 1.08	unconstrained · MANE · 14 kb · p 0.083 · regional, not allelic
Overall
CADD	22.9	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 0.669% African / African-American · 502/75,000 alleles

Filtering AF 0.621% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.602%

Overall 0.0431% 696/1,613,694 alleles · rare

Ancestry group	Frequency	1 in
African / African-Americangrpmax	0.669%	149
Admixed American	0.0533%	1,875
Remaining individualsnot grpmax-eligible	0.0384%	2,604
European (non-Finnish)	0.0114%	8,739
Finnishnot grpmax-eligible	0.00469%	21,310

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: CTSE
Protein: p.Val248Phe
Coding: c.742G>T
MANE Select: NM_001910
Type: single nucleotide variant
Location: chr1:206013815 (GRCh38)
Gene constraint: LOEUF 1.183 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 87.31 · 1 PDB
Residue 248: a β-strand; the peptidase a1 domain

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

Similar variants

CTSE p.Gly80Asp Uncertain significance ★★ ⚠ same type
CTSE p.Ala206Thr Uncertain significance ★ ⚠ same type
CTSE p.Ala259Pro Uncertain significance ★ ⚠ same type
CTSE p.Arg23Ser Uncertain significance ★ ⚠ same type
CTSE p.Arg23Trp Uncertain significance ★ ⚠ same type
CTSE p.Arg28Ser Uncertain significance ★ ⚠ same type
CTSE p.Arg37Gln Uncertain significance ★ ⚠ same type
CTSE p.Arg37Trp 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/ctse-p-val248phe (accessed [today's date]).

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