Is TACSTD2 p.Arg245= (c.735C>T) pathogenic?

TACSTD2 p.Arg245= (c.735C>T) is classified Conflicting classifications of pathogenicity in TACSTD2 (ClinVar, Conflicting submitters, 2 submitters; last evaluated 2018-11-03). Ultra-rare (popmax 0.0181%, nfe); Associated with gelatinous drop-like corneal dystrophy.

What condition is associated with TACSTD2 p.Arg245= (c.735C>T)?

TACSTD2 p.Arg245= (c.735C>T) is associated with gelatinous drop-like corneal dystrophy (ClinVar).

How common is TACSTD2 p.Arg245= (c.735C>T) in the general population?

TACSTD2 p.Arg245= (c.735C>T) is ultra-rare (popmax 0.0181%, nfe) (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.Arg245=

c.735C>T · rs145491347 · VCV715494

Conflicting classifications of pathogenicity Conflicting submitters

Classification

Conflicting classifications of pathogenicity

ClinVar

Review

Conflicting submitters ★☆☆☆

ClinVar · 2 submitters

gnomAD v4.1

Rare

ultra-rare (popmax 0.0181%, nfe)

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	<0.2	no splice effect predicted · four deltas, not one · how we know
Constraint at this position
Conservation	phyloP 0.5	GERP -4.5, phastCons 0.78
Overall
CADD	14.13	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.0181% European (non-Finnish) · 214/1,179,908 alleles

Filtering AF 0.0161% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.0153%

Overall 0.0143% 231/1,613,660 alleles · ultra-rare exomes 217/1,461,414 · genomes 14/152,246 · joint denominator

Ancestry group	Frequency	1 in
European (non-Finnish)grpmax	0.0181%	5,514
Admixed American	0.015%	6,662
Remaining individualsnot grpmax-eligible	0.00961%	10,408
African / African-American	0.00267%	37,470

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.Arg245=
Coding: c.735C>T
MANE Select: NM_002353
dbSNP: rs145491347
Type: single nucleotide variant
Location: chr1:58576422 (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 p.Arg245Cys Uncertain significance ★ ⚠ same residue
TACSTD2 p.Arg245Gly Uncertain significance ★ ⚠ same residue
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

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-arg245 (accessed [today's date]).

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