Is TACSTD2 c.*421A>G pathogenic?

TACSTD2 c.421A>G is classified Benign in TACSTD2 (ClinVar, Multiple submitters, 2 submitters; last evaluated 2018-01-12). Common (popmax 18.8%, afr) — too common for a highly-penetrant pathogenic allele; Associated with gelatinous drop-like corneal dystrophy.

What condition is associated with TACSTD2 c.*421A>G?

TACSTD2 c.*421A>G is associated with gelatinous drop-like corneal dystrophy (ClinVar).

How is Gelatinous drop-like corneal dystrophy inherited?

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

TACSTD2 c.*421A>G

Q: How common is TACSTD2 c.*421A>G in the general population?

TACSTD2 c.*421A>G is common (popmax 18.8%, afr) — too common for a highly-penetrant pathogenic allele (gnomAD).

rs9583 · VCV297754

Benign Multiple submitters

Classification

Benign

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 2 submitters

gnomAD v4.1

Common

common (popmax 18.8%, afr) — too common for a highly-penetrant pathogenic allele

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 0.001	GERP 0.89
Non-coding constraint	Z 0.01	1 kb window · o/e 1.00 · regional · uncalibrated
Overall
CADD	11.1	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 18.8% African / African-American · 7,891/41,902 alleles

Filtering AF 18.5% ClinGen BA1/BS1 input FAF95, joint · FAF99 18.3%

Overall 11.1% 20,641/186,476 alleles · common exomes 2,600/34,280 · genomes 18,041/152,196 · joint denominator

Ancestry group	Frequency	1 in
African / African-Americangrpmax	18.8%	5
Amishnot grpmax-eligible	15.6%	6
Middle Eastern	15.1%	7
Remaining individualsnot grpmax-eligible	10.8%	9
Ashkenazi Jewishnot grpmax-eligible	10.7%	9
European (non-Finnish)	9.65%	10
Admixed American	9.09%	11
Finnishnot grpmax-eligible	7.63%	13
South Asian	5.58%	18
East Asian	0.207%	482

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.*421A>G
MANE Select: NM_002353
dbSNP: rs9583
Type: single nucleotide variant
Location: chr1:58575764 (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-421a-g (accessed [today's date]).

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