Is TTC8 p.Leu415Phe (c.1245G>T) pathogenic?

TTC8 p.Leu415Phe (c.1245G>T) is classified Uncertain significance in TTC8 (ClinVar, Single submitter, 1 submitter; last evaluated 2024-09-25). Very rare (popmax 8.48e-05%, nfe); Associated with Inborn genetic diseases.

What condition is associated with TTC8 p.Leu415Phe (c.1245G>T)?

TTC8 p.Leu415Phe (c.1245G>T) is associated with Inborn genetic diseases (ClinVar).

How common is TTC8 p.Leu415Phe (c.1245G>T) in the general population?

TTC8 p.Leu415Phe (c.1245G>T) is very rare (popmax 8.48e-05%, nfe) (gnomAD).

TTC8 p.Leu415Phe

c.1245G>T · VCV3463504

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

gnomAD v4.1

Rare

very rare (popmax 8.48e-05%, nfe)

Conditions

Inborn genetic diseases

Computational evidence

Protein change
Missense predictors do not apply to this variant type; conservation carries the signal.
REVEL	0.232	benign-leaning
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 6.6	GERP 1, phastCons 1
Regional constraint	o/e 0.98	unconstrained · MANE · 53 kb · p 0.62 · regional, not allelic
Overall
CADD	23.6	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 8.48e-05% European (non-Finnish) · 1/1,179,890 alleles

Overall 6.2e-05% 1/1,613,838 alleles · very rare exomes 1/1,461,662 · genomes 0/152,176 · joint denominator

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: TTC8
Protein: p.Leu415Phe
Coding: c.1245G>T
MANE Select: NM_144596
Type: single nucleotide variant
Location: chr14:88872350 (GRCh38)
Gene constraint: LOEUF 0.8 · pLI <0.01 · ClinGen HI gene assoc. with recessive phenotype (gnomAD)
Structure: AlphaFold pLDDT 84.48

Full TTC8 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

Similar variants

TTC8 p.Ala108Thr Uncertain significance ★★ same condition
TTC8 p.Ala194Thr Uncertain significance ★★ same condition
TTC8 p.Ala461Val Uncertain significance ★★ same condition
TTC8 p.Ala55Thr Uncertain significance ★★ same condition
TTC8 p.Ala57Val Uncertain significance ★★ same condition
TTC8 p.Arg385His Uncertain significance ★★ same condition
TTC8 p.Arg421Thr Uncertain significance ★★ same condition
TTC8 p.Asn426Ser Uncertain significance ★★ 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/ttc8-p-leu415phe (accessed [today's date]).

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