Is TACSTD2 p.Asp218His (c.652G>C) pathogenic?

TACSTD2 p.Asp218His (c.652G>C) is classified Uncertain significance in TACSTD2 (ClinVar, Single submitter, 1 submitter; last evaluated 2025-06-10). AlphaMissense: likely pathogenic (0.9078); Absent from gnomAD v4.1.

How common is TACSTD2 p.Asp218His (c.652G>C) in the general population?

TACSTD2 p.Asp218His (c.652G>C) is absent from gnomAD v4.1 (gnomAD).

What do computational predictors say about TACSTD2 p.Asp218His (c.652G>C)?

AlphaMissense predicts likely pathogenic (score 0.9078) — an in-silico prediction, not a clinical call.

TACSTD2 p.Asp218His

c.652G>C · VCV3965044

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely pathogenic

0.9078 · ACMG-weighted

gnomAD v4.1

Absent

absent from gnomAD v4.1

Missense predictors

3/3 damaging

AlphaMissense, REVEL, SaProt

Computational evidence

Protein change
AlphaMissense	0.9078	likely pathogenic
REVEL	0.865	moderately pathogenic-leaning
SaProt	LLR -10.96	damaging
⇒ AlphaMissense, REVEL and SaProt all call this damaging.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 7.4	GERP 1.1, phastCons 1
Regional constraint	o/e 1.08	unconstrained · MANE · 968 bp · p 0.067 · regional, not allelic
Overall
CADD	27.6	PHRED · no single calibrated threshold — expert panels disagree

ClinVar classifies this uncertain; the computational predictors unanimously lean damaging — 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

Absent from gnomAD v4.1. Not observed in any sequenced alleles — a rarity signal (ACMG PM2-supporting), not evidence of pathogenicity on its own.

Variant & gene context

Gene: TACSTD2
Protein: p.Asp218His
Coding: c.652G>C
MANE Select: NM_002353
Type: single nucleotide variant
Location: chr1:58576505 (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 218: an α-helix

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

Similar variants

TACSTD2 p.Asp218Gly Uncertain significance ★ ⚠ same residue
TACSTD2 p.Asp218fs Pathogenic ★ 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

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-asp218his (accessed [today's date]).

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