Is TACSTD2 p.Arg3Pro (c.8G>C) pathogenic?

TACSTD2 p.Arg3Pro (c.8G>C) is classified Uncertain significance in TACSTD2 (ClinVar, Single submitter, 1 submitter; last evaluated 2018-01-13). AlphaMissense: likely benign (0.0882); Ultra-rare (popmax 0.024%, eas); Associated with gelatinous drop-like corneal dystrophy.

What condition is associated with TACSTD2 p.Arg3Pro (c.8G>C)?

TACSTD2 p.Arg3Pro (c.8G>C) is associated with gelatinous drop-like corneal dystrophy (ClinVar).

How common is TACSTD2 p.Arg3Pro (c.8G>C) in the general population?

TACSTD2 p.Arg3Pro (c.8G>C) is ultra-rare (popmax 0.024%, eas) (gnomAD).

How is Gelatinous drop-like corneal dystrophy inherited?

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

What do computational predictors say about TACSTD2 p.Arg3Pro (c.8G>C)?

AlphaMissense predicts likely benign (score 0.0882) — an in-silico prediction, not a clinical call.

TACSTD2 p.Arg3Pro

c.8G>C · rs1041904445 · VCV874796

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.0882 · ACMG-weighted

gnomAD v4.1

Rare

ultra-rare (popmax 0.024%, eas)

Missense predictors

0/3 damaging

AlphaMissense, REVEL, SaProt

Conditions

gelatinous drop-like corneal dystrophy

Computational evidence

Protein change
AlphaMissense	0.0882	likely benign
REVEL	0.201	benign-leaning
SaProt	LLR -5.43	tolerated
⇒ AlphaMissense, REVEL and SaProt all call this tolerated.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 1.7	GERP 0.35, phastCons 0.89
Regional constraint	o/e 1.08	unconstrained · MANE · 968 bp · p 0.067 · regional, not allelic
Overall
CADD	21.5	PHRED · no single calibrated threshold — expert panels disagree

ClinVar classifies this uncertain; the computational predictors unanimously lean tolerated — a triage signal, not a reclassification

AlphaMissense carries the ACMG weight for missense; REVEL and SaProt are independent agreement signals.

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.024% East Asian · 8/33,266 alleles

Filtering AF 0.0119% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.00872%

Overall 0.0016% 22/1,377,378 alleles · ultra-rare exomes 17/1,225,278 · genomes 5/152,100 · joint denominator

Ancestry group	Frequency	1 in
East Asiangrpmax	0.024%	4,158
African / African-American	0.0107%	9,315
Remaining individualsnot grpmax-eligible	0.0019%	52,534
European (non-Finnish)	0.000557%	179,420

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.Arg3Pro
Coding: c.8G>C
MANE Select: NM_002353
dbSNP: rs1041904445
Type: single nucleotide variant
Location: chr1:58577149 (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-p-arg3pro (accessed [today's date]).

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