Is TACSTD2 c.*59A>C pathogenic?

TACSTD2 c.59A>C is classified Uncertain significance in TACSTD2 (ClinVar, Single submitter, 1 submitter; last evaluated 2018-01-13). Very rare (popmax 0.00273%, afr); Associated with gelatinous drop-like corneal dystrophy.

What condition is associated with TACSTD2 c.*59A>C?

TACSTD2 c.*59A>C is associated with gelatinous drop-like corneal dystrophy (ClinVar).

How common is TACSTD2 c.*59A>C in the general population?

TACSTD2 c.*59A>C is very rare (popmax 0.00273%, afr) (gnomAD).

How is Gelatinous drop-like corneal dystrophy inherited?

Typically Autosomal recessive (Orphanet). A genetic counselor can assess individual risk for a family.

TACSTD2 c.*59A>C

rs886046456 · VCV297762

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

gnomAD v4.1

Rare

very rare (popmax 0.00273%, afr)

Conditions

gelatinous drop-like corneal dystrophy

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 -3.7	GERP -4.1
Overall
CADD	5.251	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.00273% African / African-American · 2/73,302 alleles

Filtering AF 0.000453% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.00017%

Overall 0.000506% 8/1,581,258 alleles · very rare exomes 6/1,429,070 · genomes 2/152,188 · joint denominator

Ancestry group	Frequency	1 in
African / African-Americangrpmax	0.00273%	36,651
Remaining individualsnot grpmax-eligible	0.00164%	61,034
European (non-Finnish)	0.000429%	233,088

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: TACSTD2
Coding: c.*59A>C
MANE Select: NM_002353
dbSNP: rs886046456
Type: single nucleotide variant
Location: chr1:58576126 (GRCh38)
Gene constraint: LOEUF 1.868 · pLI <0.01 · ClinGen HI gene assoc. with recessive phenotype (gnomAD)
Structure: AlphaFold pLDDT 83.11 · 7 PDB

Full TACSTD2 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Disease context

gelatinous drop-like corneal dystrophy — disease report on Sugi Atlas → Associated genes, phenotypes, clinical trials & treatments

For Gelatinous drop-like corneal dystrophy (Orphanet):

Inheritance: Autosomal recessive
Onset: Childhood
Prevalence: 1-9 / 1 000 000 (Japan)

Similar variants

TACSTD2 c.-56C>G Uncertain significance ★★ same condition
TACSTD2 p.Gly276Asp Uncertain significance ★★ ⚠ same condition
TACSTD2 p.Gly59Ser Uncertain significance ★★ ⚠ same condition
TACSTD2 c.-169G>A Benign ★★ same condition
TACSTD2 c.-54A>C Benign ★★ same condition
TACSTD2 c.*202A>G Benign ★★ same condition
TACSTD2 c.*280T>C Benign ★★ same condition
TACSTD2 c.*396T>C Likely benign ★★ 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/tacstd2-c-star-59a-c (accessed [today's date]).

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