Is TACSTD2 p.Glu147Asp (c.441G>C) pathogenic?

TACSTD2 p.Glu147Asp (c.441G>C) is classified Benign in TACSTD2 (ClinVar, Multiple submitters, 3 submitters; last evaluated 2026-01-26). AlphaMissense: likely benign (0.1644); Common (popmax 6.56%, afr) — too common for a highly-penetrant pathogenic allele; Associated with gelatinous drop-like corneal dystrophy.

What condition is associated with TACSTD2 p.Glu147Asp (c.441G>C)?

TACSTD2 p.Glu147Asp (c.441G>C) 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.

What do computational predictors say about TACSTD2 p.Glu147Asp (c.441G>C)?

AlphaMissense predicts likely benign (score 0.1644) — an in-silico prediction, not a clinical call.

TACSTD2 p.Glu147Asp

Q: How common is TACSTD2 p.Glu147Asp (c.441G>C) in the general population?

TACSTD2 p.Glu147Asp (c.441G>C) is common (popmax 6.56%, afr) — too common for a highly-penetrant pathogenic allele (gnomAD).

c.441G>C · rs1062964 · VCV297770

Benign Multiple submitters

Classification

Benign

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 3 submitters

AlphaMissense

likely benign

0.1644 · ACMG-weighted

gnomAD v4.1

Common

common (popmax 6.56%, afr) — too common for a highly-penetrant pathogenic allele

Missense predictors

0/3 damaging

AlphaMissense, REVEL, SaProt

Conditions

gelatinous drop-like corneal dystrophy

Computational evidence

Protein change
AlphaMissense	0.1644	likely benign
REVEL	0.161	moderately benign-leaning
SaProt	LLR -3.56	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 0.55	GERP -1.9, phastCons 1
Regional constraint	o/e 1.08	unconstrained · MANE · 968 bp · p 0.067 · regional, not allelic
Overall
CADD	20.8	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 6.56% African / African-American · 4,926/75,038 alleles

Filtering AF 6.41% ClinGen BA1/BS1 input FAF95, joint · FAF99 6.35%

Overall 4.96% 79,473/1,600,948 alleles · common exomes 72,104/1,448,630 · genomes 7,369/152,318 · joint denominator

Ancestry group	Frequency	1 in
Ashkenazi Jewishnot grpmax-eligible	7.64%	13
African / African-Americangrpmax	6.56%	15
European (non-Finnish)	5.33%	19
Remaining individualsnot grpmax-eligible	4.6%	22
South Asian	4.03%	25
Middle Eastern	3.37%	30
Finnishnot grpmax-eligible	3.14%	32
Amishnot grpmax-eligible	2.75%	36
Admixed American	1.71%	59
East Asian	0.00892%	11,207

Ashkenazi Jewish shows a higher raw frequency than the grpmax group above it. gnomAD excludes bottlenecked groups — Finnish, Ashkenazi Jewish, Amish and “Remaining individuals” — from grpmax, because founder effects make their frequencies unrepresentative for filtering. The table is sorted by frequency, so an excluded group can sit above the grpmax row.

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.Glu147Asp
Coding: c.441G>C
MANE Select: NM_002353
dbSNP: rs1062964
Type: single nucleotide variant
Location: chr1:58576716 (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 147: a UniProt-annotated variant site (in)

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-glu147asp (accessed [today's date]).

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