Is TBCD p.Arg360His (c.1079G>A) pathogenic?

TBCD p.Arg360His (c.1079G>A) is classified Uncertain significance in TBCD (ClinVar, Single submitter, 1 submitter; last evaluated 2023-12-05). AlphaMissense: likely benign (0.0628); Very rare (popmax 0.00934%, afr).

How common is TBCD p.Arg360His (c.1079G>A) in the general population?

TBCD p.Arg360His (c.1079G>A) is very rare (popmax 0.00934%, afr) (gnomAD).

What do computational predictors say about TBCD p.Arg360His (c.1079G>A)?

AlphaMissense predicts likely benign (score 0.0628) — an in-silico prediction, not a clinical call.

TBCD p.Arg360His

c.1079G>A · rs756514766 · VCV2962014

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.0628 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 0.00934%, afr)

Missense predictors

0/3 damaging

AlphaMissense, REVEL, SaProt

Computational evidence

Protein change
AlphaMissense	0.0628	likely benign
REVEL	0.064	moderately benign-leaning
SaProt	LLR -5.15	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 1	GERP -2.3, phastCons 0.28
Regional constraint	o/e 0.90	unconstrained · MANE · 190 kb · p 9.5e-05 · regional, not allelic
Overall
CADD	18.56	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

Grpmax group 0.00934% African / African-American · 7/74,932 alleles

Filtering AF 0.00437% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.00309%

Overall 0.00211% 34/1,613,582 alleles · very rare exomes 31/1,461,396 · genomes 3/152,186 · joint denominator

Ancestry group	Frequency	1 in
African / African-Americangrpmax	0.00934%	10,705
East Asian	0.00223%	44,890
European (non-Finnish)	0.00212%	47,188
Finnishnot grpmax-eligible	0.00156%	63,942

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: TBCD
Protein: p.Arg360His
Coding: c.1079G>A
MANE Select: NM_005993
dbSNP: rs756514766
Type: single nucleotide variant
Location: chr17:82806003 (GRCh38)
Gene constraint: LOEUF 0.763 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 90.45 · 6 PDB

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

Similar variants

TBCD p.Arg360Cys Uncertain significance ★ ⚠ same residue
TBCD c.1224-2A>G Pathogenic/Likely pathogenic ★★ same type
TBCD c.2007-2A>G Likely pathogenic ★★ same type
TBCD p.Ala475Thr Pathogenic/Likely pathogenic ★★ same type
TBCD p.Ala554Val Pathogenic/Likely pathogenic ★★ same type
TBCD p.Arg113Ter Pathogenic/Likely pathogenic ★★ same type
TBCD p.Arg303Ter Pathogenic/Likely pathogenic ★★ same type
TBCD p.Arg323Ter Pathogenic/Likely pathogenic ★★ 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/tbcd-p-arg360his (accessed [today's date]).

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