Is TTC8 p.Ile119= (c.357T>C) pathogenic?

TTC8 p.Ile119= (c.357T>C) is classified Likely benign in TTC8 (ClinVar, Multiple submitters, 3 submitters; last evaluated 2026-01-14). Ultra-rare (popmax 0.0944%, sas); Associated with Bardet-Biedl syndrome.

What condition is associated with TTC8 p.Ile119= (c.357T>C)?

TTC8 p.Ile119= (c.357T>C) is associated with Bardet-Biedl syndrome (ClinVar).

How common is TTC8 p.Ile119= (c.357T>C) in the general population?

TTC8 p.Ile119= (c.357T>C) is ultra-rare (popmax 0.0944%, sas) (gnomAD).

How is Bardet-Biedl syndrome inherited?

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

TTC8 p.Ile119=

c.357T>C · rs567203939 · VCV415628

Likely benign Multiple submitters

Classification

Likely benign

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 3 submitters

gnomAD v4.1

Rare

ultra-rare (popmax 0.0944%, sas)

Conditions

Bardet-Biedl syndrome

Computational evidence

Protein change
Missense predictors do not apply to this variant type; conservation carries the signal.
REVEL	0.115	moderately benign-leaning
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP -0.24	GERP 0.23, phastCons 0.48
Overall
CADD	7.954	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.0944% South Asian · 86/91,082 alleles

Filtering AF 0.0782% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.0723%

Overall 0.00905% 146/1,614,076 alleles · ultra-rare

Ancestry group	Frequency	1 in
South Asiangrpmax	0.0944%	1,059
Middle Eastern	0.066%	1,516
Remaining individualsnot grpmax-eligible	0.0128%	7,813
European (non-Finnish)	0.0039%	25,652
East Asian	0.00223%	44,886
African / African-American	0.00133%	75,002

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.Ile119=
Coding: c.357T>C
MANE Select: NM_144596
dbSNP: rs567203939
Type: single nucleotide variant
Location: chr14:88841064 (GRCh38)
Gene constraint: LOEUF 0.8 · pLI <0.01 · ClinGen HI gene assoc. with recessive phenotype (gnomAD)
Structure: AlphaFold pLDDT 84.48
Residue 119: the 'disordered' region

Full TTC8 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Disease context

Bardet-Biedl syndrome — disease report on Sugi Atlas → Associated genes, phenotypes, clinical trials & treatments

For Bardet-Biedl syndrome (Orphanet):

Inheritance: Autosomal recessive, Oligogenic
Onset: Antenatal, Childhood, Infancy, Neonatal
Prevalence: 1-9 / 100 000 (Specific population)

Similar variants

TTC8 p.Ile119Val Uncertain significance ★★ same residue
TTC8 c.114+2T>C Pathogenic/Likely pathogenic ★★ same condition
TTC8 c.265+1G>A Pathogenic/Likely pathogenic ★★ same condition
TTC8 c.799-2A>G Likely pathogenic ★★ same condition
TTC8 p.Gln187Ter Pathogenic/Likely pathogenic ★★ same condition
TTC8 p.Gln247Ter Pathogenic/Likely pathogenic ★★ same condition
TTC8 p.Gln86Ter Pathogenic ★★ same condition
TTC8 p.Thr163= 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/ttc8-p-ile119 (accessed [today's date]).

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