Is TBCB p.Ser207= (c.621T>C) pathogenic?

TBCB p.Ser207= (c.621T>C) is classified Likely benign in TBCB (ClinVar, Single submitter, 1 submitter; last evaluated 2025-11-26). Very rare (popmax 0.000172%, nfe).

How common is TBCB p.Ser207= (c.621T>C) in the general population?

TBCB p.Ser207= (c.621T>C) is very rare (popmax 0.000172%, nfe) (gnomAD).

TBCB p.Ser207=

c.621T>C · VCV4593252

Likely benign Single submitter

Classification

Likely benign

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

gnomAD v4.1

Rare

very rare (popmax 0.000172%, nfe)

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 -1.3	GERP -3.8, phastCons 0.001
Overall
CADD	6.869	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.000172% European (non-Finnish) · 2/1,162,608 alleles

Filtering AF 2.9e-05% ClinGen BA1/BS1 input FAF95, joint · FAF99 1.1e-05%

Overall 0.000126% 2/1,582,746 alleles · very rare exomes 2/1,430,554 · genomes 0/152,192 · joint denominator

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: TBCB
Protein: p.Ser207=
Coding: c.621T>C
MANE Select: NM_001281
Type: single nucleotide variant
Location: chr19:36125668 (GRCh38)
Gene constraint: LOEUF 1.073 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 92.55
Residue 207: the cap-gly domain

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

Similar variants

TBCB p.Tyr197Asn Uncertain significance ★★ ⚠ same type
TBCB p.Ala218Gly Uncertain significance ★ ⚠ same type
TBCB p.Arg103Gly Uncertain significance ★ ⚠ same type
TBCB p.Arg103Pro Uncertain significance ★ ⚠ same type
TBCB p.Arg138Gln Uncertain significance ★ ⚠ same type
TBCB p.Arg148His Uncertain significance ★ ⚠ same type
TBCB p.Arg196Cys Uncertain significance ★ ⚠ same type
TBCB p.Arg212Cys Uncertain significance ★ ⚠ 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/tbcb-p-ser207 (accessed [today's date]).

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