Is TACSTD2 p.Ala78Val (c.233C>T) pathogenic?

TACSTD2 p.Ala78Val (c.233C>T) is classified Uncertain significance in TACSTD2 (ClinVar, Single submitter, 1 submitter; last evaluated 2024-10-24). AlphaMissense: ambiguous (0.4758); No allele count reported in gnomAD v4.1 (AN 1,586,446).

How common is TACSTD2 p.Ala78Val (c.233C>T) in the general population?

TACSTD2 p.Ala78Val (c.233C>T) is no allele count reported in gnomAD v4.1 (AN 1,586,446) (gnomAD).

What do computational predictors say about TACSTD2 p.Ala78Val (c.233C>T)?

AlphaMissense predicts ambiguous (score 0.4758) — an in-silico prediction, not a clinical call.

TACSTD2 p.Ala78Val

c.233C>T · VCV3452521

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

ambiguous

0.4758 · ACMG-weighted

gnomAD v4.1

Not reported

no allele count reported in gnomAD v4.1 (AN 1,586,446)

Computational evidence

Protein change
AlphaMissense	0.4758	ambiguous
REVEL	0.429	indeterminate
SaProt	LLR -7.82	tolerated
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 11	GERP 2.2, phastCons 1
Regional constraint	o/e 1.08	unconstrained · MANE · 968 bp · p 0.067 · regional, not allelic
Overall
CADD	33.0	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

No allele count reported in gnomAD v4.1 (AN 1,586,446). This is missing data, not an absence: the variant may or may not be present in gnomAD. Rarity (ACMG PM2) and BA1/BS1 cannot be assessed for it.

Variant & gene context

Gene: TACSTD2
Protein: p.Ala78Val
Coding: c.233C>T
MANE Select: NM_002353
Type: single nucleotide variant
Location: chr1:58576924 (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 78: an α-helix; the thyroglobulin type-1 domain

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

Similar variants

TACSTD2 p.Ala78Glu Uncertain significance ★ ⚠ same residue
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-ala78val (accessed [today's date]).

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