Is TACSTD2 p.Asp218fs (c.653del) pathogenic?

TACSTD2 p.Asp218fs (c.653del) is classified Pathogenic in TACSTD2 (ClinVar, Single submitter, 1 submitter). Very rare (popmax 0.00267%, afr); Associated with gelatinous drop-like corneal dystrophy.

What condition is associated with TACSTD2 p.Asp218fs (c.653del)?

TACSTD2 p.Asp218fs (c.653del) is associated with gelatinous drop-like corneal dystrophy (ClinVar).

How common is TACSTD2 p.Asp218fs (c.653del) in the general population?

TACSTD2 p.Asp218fs (c.653del) is very rare (popmax 0.00267%, 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 p.Asp218fs

c.653del · rs780819073 · VCV1699935

Pathogenic Single submitter

Classification

Pathogenic

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

Consequence

frameshift

predicted LoF

gnomAD v4.1

Rare

very rare (popmax 0.00267%, afr)

Conditions

gelatinous drop-like corneal dystrophy

Computational evidence

Protein change
Missense predictors do not apply to this variant type; conservation carries the signal.
Consequence	frameshift	predicted loss-of-function
NMD	escapes	premature termination codon in the last exon (1 of 1) — the truncated protein is likely expressed. PVS1 input, not an applied code
Splicing
SpliceAI	—	not assessed · substitutions only
Constraint at this position
Conservation	phyloP 4.3	GERP -4.1, phastCons 1
Overall
CADD	33.0	PHRED · no single calibrated threshold — expert panels disagree

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

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.00267% African / African-American · 2/74,912 alleles

Filtering AF 0.000443% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.000211%

Overall 0.00062% 10/1,613,078 alleles · very rare exomes 7/1,460,858 · genomes 3/152,220 · joint denominator

Ancestry group	Frequency	1 in
African / African-Americangrpmax	0.00267%	37,456
European (non-Finnish)	0.000678%	147,467

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
Protein: p.Asp218fs
Coding: c.653del
MANE Select: NM_002353
dbSNP: rs780819073
Type: Deletion
Location: chr1:58576504 (GRCh38)
Gene constraint: LOEUF 1.868 · pLI <0.01 · ClinGen HI gene assoc. with recessive phenotype (gnomAD)
Structure: AlphaFold pLDDT 83.11 · 7 PDB
Residue 218: an α-helix

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 p.Asp218Gly Uncertain significance ★ ⚠ same residue
TACSTD2 p.Asp218His Uncertain significance ★ ⚠ same residue
TACSTD2 p.Asp47_Pro49del Uncertain significance ★ same condition
TACSTD2 p.Gln211fs Pathogenic same condition
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

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-p-asp218fs (accessed [today's date]).

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