Is TBCD p.Ser158= (c.474C>T) pathogenic?

TBCD p.Ser158= (c.474C>T) is classified Benign/Likely benign in TBCD (ClinVar, Multiple submitters, 4 submitters; last evaluated 2025-01-23). Rare (popmax 0.149%, eas).

How common is TBCD p.Ser158= (c.474C>T) in the general population?

TBCD p.Ser158= (c.474C>T) is rare (popmax 0.149%, eas) (gnomAD).

TBCD p.Ser158=

c.474C>T · rs193221478 · VCV1664191

Benign/Likely benign Multiple submitters

Classification

Benign/Likely benign

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 4 submitters

gnomAD v4.1

Rare

rare (popmax 0.149%, eas)

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 -5.7	GERP -4.6
Overall
CADD	3.861	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.149% East Asian · 67/44,870 alleles

Filtering AF 0.121% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.11%

Overall 0.0127% 205/1,613,924 alleles · rare exomes 180/1,461,666 · genomes 25/152,258 · joint denominator

Ancestry group	Frequency	1 in
East Asiangrpmax	0.149%	670
Remaining individualsnot grpmax-eligible	0.0464%	2,155
South Asian	0.0384%	2,602
European (non-Finnish)	0.00593%	16,855
Admixed American	0.005%	20,005
Finnishnot grpmax-eligible	0.00156%	64,010

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.Ser158=
Coding: c.474C>T
MANE Select: NM_005993
dbSNP: rs193221478
Type: single nucleotide variant
Location: chr17:82768458 (GRCh38)
Gene constraint: LOEUF 0.763 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 90.45 · 6 PDB

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

Similar variants

TBCD p.Ser158Cys Uncertain significance ★ ⚠ same residue
TBCD p.Ser158Phe Uncertain significance ★ ⚠ same residue
ZNF750 p.Arg158Trp Uncertain significance ★ same residue
ZNF750 p.Arg158Gln Benign same residue
TBCD c.1224-2A>G Pathogenic/Likely pathogenic ★★ same type
TBCD c.2007-2A>G Likely pathogenic ★★ same type
TBCD p.Ala475Thr Pathogenic/Likely pathogenic ★★ same type
TBCD p.Ala554Val Pathogenic/Likely pathogenic ★★ 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/tbcd-p-ser158 (accessed [today's date]).

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