Is TBL3 p.Ser278Pro (c.832T>C) pathogenic?

TBL3 p.Ser278Pro (c.832T>C) is classified Uncertain significance in TBL3 (ClinVar, Single submitter, 1 submitter; last evaluated 2022-06-03). AlphaMissense: ambiguous (0.3668); Absent from gnomAD v4.1.

How common is TBL3 p.Ser278Pro (c.832T>C) in the general population?

TBL3 p.Ser278Pro (c.832T>C) is absent from gnomAD v4.1 (gnomAD).

What do computational predictors say about TBL3 p.Ser278Pro (c.832T>C)?

AlphaMissense predicts ambiguous (score 0.3668) — an in-silico prediction, not a clinical call.

TBL3 p.Ser278Pro

c.832T>C · rs2548258684 · VCV2293573

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

ambiguous

0.3668 · ACMG-weighted

gnomAD v4.1

Absent

absent from gnomAD v4.1

Missense predictors

1/2 damaging

REVEL, SaProt · AlphaMissense indeterminate

Computational evidence

Protein change
AlphaMissense	0.3668	ambiguous
REVEL	0.225	benign-leaning
SaProt	LLR -12.47	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 7.8	GERP 1.6, phastCons 1
Regional constraint	o/e 1.08	unconstrained · MANE · 6,517 bp · p 0.0069 · regional, not allelic
Overall
CADD	26.2	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

Absent from gnomAD v4.1. Not observed in any sequenced alleles — a rarity signal (ACMG PM2-supporting), not evidence of pathogenicity on its own.

Variant & gene context

Gene: TBL3
Protein: p.Ser278Pro
Coding: c.832T>C
MANE Select: NM_006453
dbSNP: rs2548258684
Type: single nucleotide variant
Location: chr16:1975555 (GRCh38)
Gene constraint: LOEUF 0.885 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 84.48 · 3 PDB
Residue 278: a turn

Full TBL3 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Similar variants

NOXO1 p.Ala278Val Uncertain significance ★ ⚠ same residue
TBL3 c.1742+8G>C Benign ★★ same type
TBL3 p.Arg86= Benign ★★ same type
NOXO1 c.223+1G>C Uncertain significance ★ ⚠ same type
NOXO1 p.Gly312Asp Uncertain significance ★ ⚠ same type
TBL3 p.Ala106Thr Uncertain significance ★ ⚠ same type
TBL3 p.Ala106Val Uncertain significance ★ same type
TBL3 p.Ala158Gly 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/tbl3-p-ser278pro (accessed [today's date]).

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