Is TBC1D24 p.Pro93= (c.279C>T) pathogenic?

TBC1D24 p.Pro93= (c.279C>T) is classified Likely benign in TBC1D24 (ClinVar, Multiple submitters, 2 submitters; last evaluated 2024-11-11). Very rare (popmax 0.00549%, sas); Associated with autosomal dominant nonsyndromic hearing loss 65.

What condition is associated with TBC1D24 p.Pro93= (c.279C>T)?

TBC1D24 p.Pro93= (c.279C>T) is associated with autosomal dominant nonsyndromic hearing loss 65, developmental and epileptic encephalopathy, 1 (ClinVar).

How common is TBC1D24 p.Pro93= (c.279C>T) in the general population?

TBC1D24 p.Pro93= (c.279C>T) is very rare (popmax 0.00549%, sas) (gnomAD).

TBC1D24 p.Pro93=

c.279C>T · rs1021608042 · VCV1637852

Likely benign Multiple submitters

Classification

Likely benign

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 2 submitters

gnomAD v4.1

Rare

very rare (popmax 0.00549%, sas)

Conditions

autosomal dominant nonsyndromic hearing loss 65

Computational evidence

Protein change
Missense predictors do not apply to this variant type; conservation carries the signal.
Splicing
SpliceAI	<0.2	no splice effect predicted · four deltas, not one · how we know
Constraint at this position
Conservation	phyloP -5.8	GERP -3.4
Overall
CADD	2.801	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.00549% South Asian · 5/91,088 alleles

Filtering AF 0.0021% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.00136%

Overall 0.00192% 31/1,612,740 alleles · very rare exomes 27/1,460,516 · genomes 4/152,224 · joint denominator

Ancestry group	Frequency	1 in
South Asiangrpmax	0.00549%	18,218
Remaining individualsnot grpmax-eligible	0.0032%	31,232
East Asian	0.00223%	44,894
European (non-Finnish)	0.00178%	56,189
Admixed American	0.00167%	60,006
African / African-American	0.00133%	74,932

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: TBC1D24
Protein: p.Pro93=
Coding: c.279C>T
MANE Select: NM_001199107
dbSNP: rs1021608042
Type: single nucleotide variant
Location: chr16:2496427 (GRCh38)
Gene constraint: LOEUF 1.214 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 84.46
Residue 93: the rab-gap tbc domain

Full TBC1D24 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Disease context

autosomal dominant nonsyndromic hearing loss 65 — disease report on Sugi Atlas → Associated genes, phenotypes, clinical trials & treatments

Also linked: developmental and epileptic encephalopathy, 1

Similar variants

TBC1D24 c.1302+1G>T Likely pathogenic ★★ same condition
TBC1D24 c.965+2T>C Pathogenic/Likely pathogenic ★★ same condition
TBC1D24 c.983+1G>C Likely pathogenic ★★ same condition
TBC1D24 p.Ala289Val Likely pathogenic ★★ same condition
TBC1D24 p.Ala39Val Pathogenic ★★ ⚠ same condition
TBC1D24 p.Ala500Val Pathogenic/Likely pathogenic ★★ same condition
TBC1D24 p.Arg227Gln Likely pathogenic ★★ same condition
TBC1D24 p.Arg227Trp Pathogenic/Likely pathogenic ★★ 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/tbc1d24-p-pro93 (accessed [today's date]).

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