Is TACSTD2 p.Ser71Pro (c.211T>C) pathogenic?

TACSTD2 p.Ser71Pro (c.211T>C) is classified Uncertain significance in TACSTD2 (ClinVar, Single submitter, 1 submitter; last evaluated 2024-08-25). AlphaMissense: likely benign (0.1197); No allele count reported in gnomAD v4.1 (AN 1,587,304).

How common is TACSTD2 p.Ser71Pro (c.211T>C) in the general population?

TACSTD2 p.Ser71Pro (c.211T>C) is no allele count reported in gnomAD v4.1 (AN 1,587,304) (gnomAD).

What do computational predictors say about TACSTD2 p.Ser71Pro (c.211T>C)?

AlphaMissense predicts likely benign (score 0.1197) — an in-silico prediction, not a clinical call.

TACSTD2 p.Ser71Pro

c.211T>C · VCV3452519

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.1197 · ACMG-weighted

gnomAD v4.1

Not reported

no allele count reported in gnomAD v4.1 (AN 1,587,304)

Missense predictors

0/3 damaging

AlphaMissense, REVEL, SaProt

Computational evidence

Protein change
AlphaMissense	0.1197	likely benign
REVEL	0.029	moderately benign-leaning
SaProt	LLR -3.90	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 1.6	GERP -2, phastCons 0.28
Regional constraint	o/e 1.08	unconstrained · MANE · 968 bp · p 0.067 · regional, not allelic
Overall
CADD	19.49	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

No allele count reported in gnomAD v4.1 (AN 1,587,304). 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.Ser71Pro
Coding: c.211T>C
MANE Select: NM_002353
Type: single nucleotide variant
Location: chr1:58576946 (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 71: 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 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
TACSTD2 c.*280T>C 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-ser71pro (accessed [today's date]).

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