Is TBC1D24 p.Phe95= (c.285C>T) pathogenic?

TBC1D24 p.Phe95= (c.285C>T) is classified Conflicting classifications of pathogenicity in TBC1D24 (ClinVar, Conflicting submitters, 3 submitters; last evaluated 2025-06-30). Ultra-rare (popmax 0.0164%, mid); Associated with Inborn genetic diseases.

What condition is associated with TBC1D24 p.Phe95= (c.285C>T)?

TBC1D24 p.Phe95= (c.285C>T) is associated with Inborn genetic diseases, developmental and epileptic encephalopathy, 1, autosomal dominant nonsyndromic hearing loss 65 (ClinVar).

How common is TBC1D24 p.Phe95= (c.285C>T) in the general population?

TBC1D24 p.Phe95= (c.285C>T) is ultra-rare (popmax 0.0164%, mid) (gnomAD).

TBC1D24 p.Phe95=

c.285C>T · rs774354974 · VCV425088

Conflicting classifications of pathogenicity Conflicting submitters

Classification

Conflicting classifications of pathogenicity

ClinVar

Review

Conflicting submitters ★☆☆☆

ClinVar · 3 submitters

gnomAD v4.1

Rare

ultra-rare (popmax 0.0164%, mid)

Conditions

Inborn genetic diseases

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 -2	GERP -3.4
Overall
CADD	6.579	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.0164% Middle Eastern · 1/6,084 alleles

Filtering AF 0.00428% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.00295%

Overall 0.00149% 24/1,612,688 alleles · ultra-rare exomes 23/1,460,444 · genomes 1/152,244 · joint denominator

Ancestry group	Frequency	1 in
Middle Easterngrpmax	0.0164%	6,084
Admixed American	0.01%	10,000
European (non-Finnish)	0.00136%	73,748
South Asian	0.0011%	91,090

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.Phe95=
Coding: c.285C>T
MANE Select: NM_001199107
dbSNP: rs774354974
Type: single nucleotide variant
Location: chr16:2496433 (GRCh38)
Gene constraint: LOEUF 1.214 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 84.46
Residue 95: 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 autosomal dominant nonsyndromic hearing loss 65

Similar variants

TBC1D24 p.Phe95Leu Uncertain significance ★ ⚠ same residue
TBC1D24 p.Phe95Ser 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

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-phe95 (accessed [today's date]).

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