Is CSTA p.Tyr35fs (c.102_103del) pathogenic?

CSTA p.Tyr35fs (c.102103del) is classified Likely pathogenic in CSTA (ClinVar, Single submitter, 1 submitter; last evaluated 2025-05-07). Very rare (popmax 0.00167%, amr).

How common is CSTA p.Tyr35fs (c.102_103del) in the general population?

CSTA p.Tyr35fs (c.102_103del) is very rare (popmax 0.00167%, amr) (gnomAD).

CSTA p.Tyr35fs

c.102_103del · rs1321015847 · VCV450304

Likely pathogenic Single submitter

Classification

Likely pathogenic

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

Consequence

frameshift

predicted LoF

gnomAD v4.1

Rare

very rare (popmax 0.00167%, amr)

Computational evidence

Protein change
Missense predictors do not apply to this variant type; conservation carries the signal.
Consequence	frameshift	predicted loss-of-function
NMD	predicted	premature termination codon in exon 2 of 3
Splicing
SpliceAI	—	not assessed · substitutions only
Constraint at this position
Conservation	phyloP -0.62	GERP -3.5

Predicted loss-of-function is descriptive, not an applied PVS1 code.

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.00167% Admixed American · 1/60,004 alleles

Overall 6.85e-05% 1/1,460,752 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: CSTA
Protein: p.Tyr35fs
Coding: c.102_103del
MANE Select: NM_005213
dbSNP: rs1321015847
Type: Deletion
Location: chr3:122337582 (GRCh38)
Gene constraint: LOEUF 1.219 · pLI 0.12 (gnomAD)
Structure: AlphaFold pLDDT 93.57 · 14 PDB
Residue 35: a β-strand

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

Similar variants

CSTA p.Tyr35= Benign ★★ same residue
CSTA p.Tyr35Ter Likely pathogenic ★ same residue

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/csta-p-tyr35fs (accessed [today's date]).

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