Is TACSTD2 p.Arg300Gln (c.899G>A) pathogenic?

TACSTD2 p.Arg300Gln (c.899G>A) is classified Conflicting classifications of pathogenicity in TACSTD2 (ClinVar, Conflicting submitters, 3 submitters; last evaluated 2022-09-22). AlphaMissense: likely benign (0.0912); Rare (popmax 0.59%, afr); Associated with gelatinous drop-like corneal dystrophy.

What condition is associated with TACSTD2 p.Arg300Gln (c.899G>A)?

TACSTD2 p.Arg300Gln (c.899G>A) is associated with gelatinous drop-like corneal dystrophy (ClinVar).

How common is TACSTD2 p.Arg300Gln (c.899G>A) in the general population?

TACSTD2 p.Arg300Gln (c.899G>A) is rare (popmax 0.59%, afr) (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.Arg300Gln (c.899G>A)?

AlphaMissense predicts likely benign (score 0.0912) — an in-silico prediction, not a clinical call.

TACSTD2 p.Arg300Gln

c.899G>A · rs142263208 · VCV873846

Conflicting classifications of pathogenicity Conflicting submitters

Classification

Conflicting classifications of pathogenicity

ClinVar

Review

Conflicting submitters ★☆☆☆

ClinVar · 3 submitters

AlphaMissense

likely benign

0.0912 · ACMG-weighted

gnomAD v4.1

Rare

rare (popmax 0.59%, afr)

Missense predictors

0/3 damaging

AlphaMissense, REVEL, SaProt

Conditions

gelatinous drop-like corneal dystrophy

Computational evidence

Protein change
AlphaMissense	0.0912	likely benign
REVEL	0.201	benign-leaning
SaProt	LLR -8.11	tolerated
⇒ AlphaMissense, REVEL and SaProt all call this tolerated.
Splicing
SpliceAI	<0.2	no splice effect predicted · four deltas, not one · how we know
Constraint at this position
Conservation	phyloP 2.1	GERP -0.7, phastCons 0.59
Regional constraint	o/e 1.08	unconstrained · MANE · 968 bp · p 0.067 · regional, not allelic
Overall
CADD	21.0	PHRED · no single calibrated threshold — expert panels disagree

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

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.59% African / African-American · 443/75,026 alleles

Filtering AF 0.545% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.527%

Overall 0.0299% 483/1,613,982 alleles · rare exomes 231/1,461,670 · genomes 252/152,312 · joint denominator

Ancestry group	Frequency	1 in
African / African-Americangrpmax	0.59%	169
Remaining individualsnot grpmax-eligible	0.0416%	2,404
Admixed American	0.0167%	6,001
South Asian	0.0011%	91,036
European (non-Finnish)	0.000254%	393,323

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.Arg300Gln
Coding: c.899G>A
MANE Select: NM_002353
dbSNP: rs142263208
Type: single nucleotide variant
Location: chr1:58576258 (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 300: 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 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-arg300gln (accessed [today's date]).

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