Is TBCE p.Ser285Phe (c.854C>T) pathogenic?

TBCE p.Ser285Phe (c.854C>T) is classified Uncertain significance in TBCE (ClinVar, Single submitter, 1 submitter; last evaluated 2021-12-03). AlphaMissense: ambiguous (0.5583); Very rare (popmax 0.00668%, eas).

How common is TBCE p.Ser285Phe (c.854C>T) in the general population?

TBCE p.Ser285Phe (c.854C>T) is very rare (popmax 0.00668%, eas) (gnomAD).

What do computational predictors say about TBCE p.Ser285Phe (c.854C>T)?

AlphaMissense predicts ambiguous (score 0.5583) — an in-silico prediction, not a clinical call.

TBCE p.Ser285Phe

c.854C>T · rs1323987506 · VCV1948363

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

ambiguous

0.5583 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 0.00668%, eas)

Missense predictors

1/2 damaging

REVEL, SaProt · AlphaMissense indeterminate

Computational evidence

Protein change
AlphaMissense	0.5583	ambiguous
REVEL	0.196	benign-leaning
SaProt	LLR -10.62	damaging
⇒ SaProt calls this damaging; REVEL does not; AlphaMissense is indeterminate.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 2.4	GERP 0.31, phastCons 0.99
Regional constraint	o/e 1.00	unconstrained · MANE · 69 kb · p 0.95 · regional, not allelic
Overall
CADD	20.5	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 0.00668% East Asian · 3/44,896 alleles

Filtering AF 0.00177% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.000891%

Overall 0.00031% 5/1,613,920 alleles · very rare exomes 4/1,461,722 · genomes 1/152,198 · joint denominator

Ancestry group	Frequency	1 in
East Asiangrpmax	0.00668%	14,965
Remaining individualsnot grpmax-eligible	0.0016%	62,484
European (non-Finnish)	8.48e-05%	1,179,934

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.Ser285Phe
Coding: c.854C>T
MANE Select: NM_003193
dbSNP: rs1323987506
Type: single nucleotide variant
Location: chr1:235436406 (GRCh38)
Gene constraint: LOEUF 0.868 · pLI <0.01 · ClinGen HI gene assoc. with recessive phenotype (gnomAD)
Structure: AlphaFold pLDDT 89.27 · 6 PDB

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

Similar variants

TBCE c.100+1G>A Pathogenic/Likely pathogenic ★★ same type
TBCE p.Arg12Ter Likely pathogenic ★★ same type
TBCE p.Gln123Ter Pathogenic/Likely pathogenic ★★ same type
TBCE p.Ile155Asn Pathogenic/Likely pathogenic ★★ same type
TBCE p.Lys145Ter Pathogenic/Likely pathogenic ★★ same type
B3GALNT2 p.Gly492Ser Uncertain significance ★★ ⚠ same type
TBCE c.738-3C>T Uncertain significance ★★ same type
TBCE c.898+5A>G 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/tbce-p-ser285phe (accessed [today's date]).

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