Is TBC1D24 p.Pro69= (c.207T>C) pathogenic?

TBC1D24 p.Pro69= (c.207T>C) is classified Benign in TBC1D24 (ClinVar, Multiple submitters, 9 submitters; last evaluated 2026-02-03). Common (popmax 19.7%, afr) — too common for a highly-penetrant pathogenic allele; Associated with Inborn genetic diseases.

What condition is associated with TBC1D24 p.Pro69= (c.207T>C)?

TBC1D24 p.Pro69= (c.207T>C) is associated with Inborn genetic diseases, developmental and epileptic encephalopathy, 1, familial infantile myoclonic epilepsy (ClinVar).

TBC1D24 p.Pro69=

Q: How common is TBC1D24 p.Pro69= (c.207T>C) in the general population?

TBC1D24 p.Pro69= (c.207T>C) is common (popmax 19.7%, afr) — too common for a highly-penetrant pathogenic allele (gnomAD).

c.207T>C · rs13339237 · VCV130539

Benign Multiple submitters

Classification

Benign

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 9 submitters

gnomAD v4.1

Common

common (popmax 19.7%, afr) — too common for a highly-penetrant pathogenic allele

Conditions

Inborn genetic diseases

Computational evidence

Protein change
Missense predictors do not apply to this variant type; conservation carries the signal.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP -13	GERP -3.4
Overall
CADD	0.023	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 19.7% African / African-American · 14,747/75,018 alleles

Filtering AF 19.4% ClinGen BA1/BS1 input FAF95, joint · FAF99 19.3%

Overall 1.2% 19,356/1,613,444 alleles · common exomes 10,560/1,461,150 · genomes 8,796/152,294 · joint denominator

Ancestry group	Frequency	1 in
African / African-Americangrpmax	19.7%	5
Admixed American	2.09%	48
Middle Eastern	2.01%	50
Remaining individualsnot grpmax-eligible	1.88%	53
Ashkenazi Jewishnot grpmax-eligible	1.18%	85
European (non-Finnish)	0.141%	711
South Asian	0.0516%	1,938
Finnishnot grpmax-eligible	0.00158%	63,346

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.Pro69=
Coding: c.207T>C
MANE Select: NM_001199107
dbSNP: rs13339237
Type: single nucleotide variant
Location: chr16:2496355 (GRCh38)
Gene constraint: LOEUF 1.214 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 84.46
Residue 69: the rab-gap tbc domain

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

Disease context

Inborn genetic diseases — disease report on Sugi Atlas → Associated genes, phenotypes, clinical trials & treatments

Also linked: developmental and epileptic encephalopathy, 1 familial infantile myoclonic epilepsy autosomal dominant nonsyndromic hearing loss 65

Similar variants

TBC1D24 p.Pro69Arg Uncertain significance ★ ⚠ same residue
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

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-pro69 (accessed [today's date]).

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