Is TFB2M p.Pro182Arg (c.545C>G) pathogenic?

TFB2M p.Pro182Arg (c.545C>G) is classified Uncertain significance in TFB2M (ClinVar, Single submitter, 1 submitter; last evaluated 2024-09-08). AlphaMissense: likely benign (0.1475); Absent from gnomAD v4.1.

How common is TFB2M p.Pro182Arg (c.545C>G) in the general population?

TFB2M p.Pro182Arg (c.545C>G) is absent from gnomAD v4.1 (gnomAD).

What do computational predictors say about TFB2M p.Pro182Arg (c.545C>G)?

AlphaMissense predicts likely benign (score 0.1475) — an in-silico prediction, not a clinical call.

TFB2M p.Pro182Arg

c.545C>G · VCV3455646

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.1475 · ACMG-weighted

gnomAD v4.1

Absent

absent from gnomAD v4.1

Missense predictors

0/3 damaging

AlphaMissense, REVEL, SaProt

Computational evidence

Protein change
AlphaMissense	0.1475	likely benign
REVEL	0.263	benign-leaning
SaProt	LLR -8.91	tolerated
⇒ AlphaMissense, REVEL and SaProt all call this tolerated.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 5.7	GERP 0.016, phastCons 1
Regional constraint	o/e 1.01	unconstrained · MANE · 25 kb · p 0.79 · regional, not allelic
Overall
CADD	22.3	PHRED · no single calibrated threshold — expert panels disagree

ClinVar classifies this uncertain; the computational predictors unanimously lean tolerated — a triage signal, not a reclassification

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: TFB2M
Protein: p.Pro182Arg
Coding: c.545C>G
MANE Select: NM_022366
Type: single nucleotide variant
Location: chr1:246557392 (GRCh38)
Gene constraint: LOEUF 1.156 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 80.89 · 12 PDB

Full TFB2M gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Similar variants

TFB2M p.Asp126= Benign ★★ same type
TFB2M p.Ala112Ser Uncertain significance ★ ⚠ same type
TFB2M p.Ala112Thr Uncertain significance ★ ⚠ same type
TFB2M p.Ala347Gly Uncertain significance ★ ⚠ same type
TFB2M p.Ala67Asp Uncertain significance ★ ⚠ same type
TFB2M p.Ala85Ser Uncertain significance ★ ⚠ same type
TFB2M p.Arg170Gly Uncertain significance ★ ⚠ same type
TFB2M p.Arg170Leu 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/tfb2m-p-pro182arg (accessed [today's date]).

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