Is TBC1D24 p.Pro358= (c.1074C>T) pathogenic?

TBC1D24 p.Pro358= (c.1074C>T) is classified Benign/Likely benign in TBC1D24 (ClinVar, Multiple submitters, 7 submitters; last evaluated 2025-12-22). Rare (popmax 0.521%, eas); Associated with developmental and epileptic encephalopathy, 1.

What condition is associated with TBC1D24 p.Pro358= (c.1074C>T)?

TBC1D24 p.Pro358= (c.1074C>T) is associated with developmental and epileptic encephalopathy, 1, familial infantile myoclonic epilepsy, autosomal dominant nonsyndromic hearing loss 65 (ClinVar).

How common is TBC1D24 p.Pro358= (c.1074C>T) in the general population?

TBC1D24 p.Pro358= (c.1074C>T) is rare (popmax 0.521%, eas) (gnomAD).

How is Infantile epileptic spasms syndrome inherited?

Typically Autosomal dominant, Autosomal recessive (Orphanet). A genetic counselor can assess individual risk for a family.

TBC1D24 p.Pro358=

c.1074C>T · rs75961715 · VCV139398

Benign/Likely benign Multiple submitters

Classification

Benign/Likely benign

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 7 submitters

gnomAD v4.1

Rare

rare (popmax 0.521%, eas)

Conditions

developmental and epileptic encephalopathy, 1

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 -5.3	GERP -3.2
Overall
CADD	2.569	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.521% East Asian · 233/44,764 alleles

Filtering AF 0.466% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.444%

Overall 0.0199% 321/1,610,412 alleles · rare exomes 279/1,458,100 · genomes 42/152,312 · joint denominator

Ancestry group	Frequency	1 in
East Asiangrpmax	0.521%	192
Ashkenazi Jewishnot grpmax-eligible	0.102%	982
Remaining individualsnot grpmax-eligible	0.0273%	3,667
African / African-American	0.008%	12,499
South Asian	0.00333%	30,053
European (non-Finnish)	0.00263%	38,014
Admixed American	0.00168%	59,622

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.Pro358=
Coding: c.1074C>T
MANE Select: NM_001199107
dbSNP: rs75961715
Type: single nucleotide variant
Location: chr16:2498328 (GRCh38)
Gene constraint: LOEUF 1.214 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 84.46
Residue 358: the tldc domain

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

Disease context

developmental and epileptic encephalopathy, 1 — disease report on Sugi Atlas → Associated genes, phenotypes, clinical trials & treatments

Also linked: familial infantile myoclonic epilepsy autosomal dominant nonsyndromic hearing loss 65

For Infantile epileptic spasms syndrome (Orphanet):

Inheritance: Autosomal dominant, Autosomal recessive, X-linked dominant

Similar variants

TBC1D24 p.Pro358Thr 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-pro358 (accessed [today's date]).

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