Is TBCE p.Cys61Ser (c.181T>A) pathogenic?

TBCE p.Cys61Ser (c.181T>A) is classified Uncertain significance in TBCE (ClinVar, Single submitter, 1 submitter; last evaluated 2025-06-07). AlphaMissense: likely pathogenic (0.7075); Ultra-rare (popmax 0.0134%, eas); Associated with Inborn genetic diseases.

What condition is associated with TBCE p.Cys61Ser (c.181T>A)?

TBCE p.Cys61Ser (c.181T>A) is associated with Inborn genetic diseases (ClinVar).

How common is TBCE p.Cys61Ser (c.181T>A) in the general population?

TBCE p.Cys61Ser (c.181T>A) is ultra-rare (popmax 0.0134%, eas) (gnomAD).

What do computational predictors say about TBCE p.Cys61Ser (c.181T>A)?

AlphaMissense predicts likely pathogenic (score 0.7075) — an in-silico prediction, not a clinical call.

TBCE p.Cys61Ser

c.181T>A · VCV3966123

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely pathogenic

0.7075 · ACMG-weighted

gnomAD v4.1

Rare

ultra-rare (popmax 0.0134%, eas)

Missense predictors

2/3 damaging

AlphaMissense, REVEL, SaProt

Conditions

Inborn genetic diseases

Computational evidence

Protein change
AlphaMissense	0.7075	likely pathogenic · top 10% in TBCE
REVEL	0.791	moderately pathogenic-leaning
SaProt	LLR -5.53	tolerated
⇒ AlphaMissense and REVEL call this damaging; SaProt does not.
Splicing
SpliceAI	<0.2	all four deltas below 0.2 · T>G here scores Δ0.48 · evaluated, not missing
Constraint at this position
Conservation	phyloP 7.6	GERP 1.4, phastCons 1
Regional constraint	o/e 1.00	unconstrained · MANE · 69 kb · p 0.95 · regional, not allelic
Overall
CADD	24.0	PHRED · no single calibrated threshold — expert panels disagree

AlphaMissense carries the ACMG weight for missense; REVEL and SaProt are independent agreement signals.

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.0134% East Asian · 6/44,866 alleles

Filtering AF 0.00579% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.00394%

Overall 0.000434% 7/1,613,258 alleles · ultra-rare exomes 4/1,460,968 · genomes 3/152,290 · joint denominator

Ancestry group	Frequency	1 in
East Asiangrpmax	0.0134%	7,478
Remaining individualsnot grpmax-eligible	0.0016%	62,458

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: TBCE
Protein: p.Cys61Ser
Coding: c.181T>A
MANE Select: NM_003193
Type: single nucleotide variant
Location: chr1:235401583 (GRCh38)
Gene constraint: LOEUF 0.868 · pLI <0.01 · ClinGen HI gene assoc. with recessive phenotype (gnomAD)
Structure: AlphaFold pLDDT 89.27 · 6 PDB
Residue 61: the cap-gly domain

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

Disease context

Inborn genetic diseases — disease report on Sugi Atlas → Associated genes, phenotypes, clinical trials & treatments

Similar variants

B3GALNT2 p.Gly492Ser Uncertain significance ★★ ⚠ same condition
TBCE c.738-3C>T Uncertain significance ★★ same condition
TBCE c.898+5A>G Uncertain significance ★★ same condition
TBCE p.Arg71His Uncertain significance ★★ same condition
TBCE p.Arg88Cys Uncertain significance ★★ ⚠ same condition
TBCE p.Asn87Thr Uncertain significance ★★ ⚠ same condition
TBCE p.Cys141Tyr Uncertain significance ★★ ⚠ same condition
TBCE p.Glu376Asp Uncertain significance ★★ ⚠ same condition

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/tbce-p-cys61ser (accessed [today's date]).

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