Is CSTA p.Tyr35= (c.105C>T) pathogenic?

CSTA p.Tyr35= (c.105C>T) is classified Benign in CSTA (ClinVar, Multiple submitters, 2 submitters; last evaluated 2018-11-10). Common (popmax 57.4%, nfe) — too common for a highly-penetrant pathogenic allele.

CSTA p.Tyr35=

Q: How common is CSTA p.Tyr35= (c.105C>T) in the general population?

CSTA p.Tyr35= (c.105C>T) is common (popmax 57.4%, nfe) — too common for a highly-penetrant pathogenic allele (gnomAD).

c.105C>T · rs17589 · VCV1297253

Benign Multiple submitters

Classification

Benign

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 2 submitters

gnomAD v4.1

Common

common (popmax 57.4%, nfe) — too common for a highly-penetrant pathogenic allele

Computational evidence

Protein change
Missense predictors do not apply to this variant type; conservation carries the signal.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP -5.9	GERP -3.5
Overall
CADD	0.388	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 57.4% European (non-Finnish) · 675,263/1,175,458 alleles

Filtering AF 57.3% ClinGen BA1/BS1 input FAF95, joint · FAF99 57.3%

Overall 54.1% 869,687/1,608,798 alleles · common

Ancestry group	Frequency	1 in
European (non-Finnish)grpmax	57.4%	2
Ashkenazi Jewishnot grpmax-eligible	55%	2
Finnishnot grpmax-eligible	54.4%	2
Middle Eastern	53%	2
Remaining individualsnot grpmax-eligible	52%	2
Admixed American	51.7%	2
Amishnot grpmax-eligible	50.3%	2
South Asian	46.7%	2
African / African-American	40.4%	2
East Asian	8.07%	12

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.Tyr35=
Coding: c.105C>T
MANE Select: NM_005213
dbSNP: rs17589
Type: single nucleotide variant
Location: chr3:122337585 (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.Tyr35Ter Likely pathogenic ★ same residue
CSTA p.Tyr35fs Likely pathogenic ★ same residue
CSTA p.Arg58Ter Likely pathogenic ★★ same type
CSTA p.Lys22Ter Pathogenic ★★ same type
CSTA c.169-12A>C Benign ★★ same type
CSTA p.Lys91Asn Benign ★★ ⚠ same type
CSTA p.Thr96Met Benign ★★ ⚠ same type
CSTA c.67-2A>T Pathogenic ★ 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/csta-p-tyr35 (accessed [today's date]).

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