Is TACSTD2 p.Pro106= (c.318C>G) pathogenic?

TACSTD2 p.Pro106= (c.318C>G) is classified Likely benign in TACSTD2 (ClinVar, No assertion criteria, 1 submitter; last evaluated 2019-03-06). Ultra-rare (popmax 0.0152%, amr); Associated with TACSTD2-related disorder.

What condition is associated with TACSTD2 p.Pro106= (c.318C>G)?

TACSTD2 p.Pro106= (c.318C>G) is associated with TACSTD2-related disorder (ClinVar).

How common is TACSTD2 p.Pro106= (c.318C>G) in the general population?

TACSTD2 p.Pro106= (c.318C>G) is ultra-rare (popmax 0.0152%, amr) (gnomAD).

TACSTD2 p.Pro106=

c.318C>G · rs756761287 · VCV3057451

Likely benign No assertion criteria

Classification

Likely benign

ClinVar

Review

No assertion criteria ☆☆☆☆

ClinVar · 1 submitter

gnomAD v4.1

Rare

ultra-rare (popmax 0.0152%, amr)

Conditions

TACSTD2-related disorder

Computational evidence

Protein change
Missense predictors do not apply to this variant type; conservation carries the signal.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP -1.5	GERP -4.4
Overall
CADD	9.811	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.0152% Admixed American · 9/59,356 alleles

Filtering AF 0.00921% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.00865%

Overall 0.00934% 149/1,595,068 alleles · ultra-rare exomes 137/1,442,950 · genomes 12/152,118 · joint denominator

Ancestry group	Frequency	1 in
Admixed Americangrpmax	0.0152%	6,595
Remaining individualsnot grpmax-eligible	0.0129%	7,762
European (non-Finnish)	0.0108%	9,272
African / African-American	0.00535%	18,694
Finnishnot grpmax-eligible	0.00199%	50,142

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.Pro106=
Coding: c.318C>G
MANE Select: NM_002353
dbSNP: rs756761287
Type: single nucleotide variant
Location: chr1:58576839 (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 106: the thyroglobulin type-1 domain

Full TACSTD2 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Disease context

TACSTD2-related disorder

Similar variants

TACSTD2 p.Ala23= Likely benign same condition
TACSTD2 c.-56C>G Uncertain significance ★★ same type
TACSTD2 p.Arg135Leu Uncertain significance ★★ ⚠ same type
TACSTD2 p.Gly276Asp Uncertain significance ★★ ⚠ same type
TACSTD2 p.Gly59Ser Uncertain significance ★★ ⚠ same type
TACSTD2 c.-169G>A Benign ★★ same type
TACSTD2 c.-54A>C Benign ★★ same type
TACSTD2 c.*202A>G Benign ★★ same type

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-pro106 (accessed [today's date]).

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