Is TBCD p.His47= (c.141C>T) pathogenic?

TBCD p.His47= (c.141C>T) is classified Likely benign in TBCD (ClinVar, Multiple submitters, 2 submitters; last evaluated 2026-01-15). Ultra-rare (popmax 0.0132%, sas).

How common is TBCD p.His47= (c.141C>T) in the general population?

TBCD p.His47= (c.141C>T) is ultra-rare (popmax 0.0132%, sas) (gnomAD).

TBCD p.His47=

c.141C>T · rs562033780 · VCV1578878

Likely benign Multiple submitters

Classification

Likely benign

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 2 submitters

gnomAD v4.1

Rare

ultra-rare (popmax 0.0132%, sas)

⚠ Built without this gene's context — gene constraint and dosage, protein structure, pathways, panels and related-variant links were not looked up for this page. why

Computational evidence

Protein change
Missense predictors do not apply to this variant type; conservation carries the signal.
Splicing
SpliceAI	—	not looked up on this page · why
Constraint at this position
Conservation	phyloP -2.5	GERP -3.3
Overall
CADD	12.78	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.0132% South Asian · 9/68,348 alleles

Filtering AF 0.00677% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.00507%

Overall 0.00505% 72/1,424,860 alleles · ultra-rare exomes 62/1,272,940 · genomes 10/151,920 · joint denominator

Ancestry group	Frequency	1 in
Ashkenazi Jewishnot grpmax-eligible	0.0438%	2,281
South Asiangrpmax	0.0132%	7,594
Remaining individualsnot grpmax-eligible	0.00732%	13,663
European (non-Finnish)	0.00436%	22,953
African / African-American	0.00151%	66,058

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: TBCD
Protein: p.His47=
Coding: c.141C>T
MANE Select: NM_005993
dbSNP: rs562033780
Type: single nucleotide variant
Location: chr17:82752334 (GRCh38)

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

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/tbcd-p-his47 (accessed [today's date]).

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