Is TBC1D24 p.Phe290= (c.870C>T) pathogenic?

TBC1D24 p.Phe290= (c.870C>T) is classified Likely benign in TBC1D24 (ClinVar, Multiple submitters, 2 submitters; last evaluated 2025-10-02). Ultra-rare (popmax 0.0121%, sas); Associated with developmental and epileptic encephalopathy, 1.

What condition is associated with TBC1D24 p.Phe290= (c.870C>T)?

TBC1D24 p.Phe290= (c.870C>T) is associated with developmental and epileptic encephalopathy, 1, autosomal dominant nonsyndromic hearing loss 65 (ClinVar).

How common is TBC1D24 p.Phe290= (c.870C>T) in the general population?

TBC1D24 p.Phe290= (c.870C>T) is ultra-rare (popmax 0.0121%, sas) (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.Phe290=

c.870C>T · rs770453630 · VCV1080983

Likely benign Multiple submitters

Classification

Likely benign

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 2 submitters

gnomAD v4.1

Rare

ultra-rare (popmax 0.0121%, sas)

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 -4	GERP -2.5
Overall
CADD	6.194	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.0121% South Asian · 11/91,076 alleles

Filtering AF 0.00676% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.00522%

Overall 0.00211% 34/1,613,766 alleles · ultra-rare exomes 34/1,461,404 · genomes 0/152,362 · joint denominator

Ancestry group	Frequency	1 in
South Asiangrpmax	0.0121%	8,280
European (non-Finnish)	0.00178%	56,193
Remaining individualsnot grpmax-eligible	0.0016%	62,506
African / African-American	0.00133%	75,066

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.Phe290=
Coding: c.870C>T
MANE Select: NM_001199107
dbSNP: rs770453630
Type: single nucleotide variant
Location: chr16:2497018 (GRCh38)
Gene constraint: LOEUF 1.214 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 84.46

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: autosomal dominant nonsyndromic hearing loss 65

For Infantile epileptic spasms syndrome (Orphanet):

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

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-phe290 (accessed [today's date]).

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