Is TTC8 p.Pro467= (c.1401G>A) pathogenic?

TTC8 p.Pro467= (c.1401G>A) is classified Conflicting classifications of pathogenicity in TTC8 (ClinVar, Conflicting submitters, 5 submitters; last evaluated 2026-02-02). Low-frequency (popmax 1.02%, afr); Associated with Bardet-Biedl syndrome.

What condition is associated with TTC8 p.Pro467= (c.1401G>A)?

TTC8 p.Pro467= (c.1401G>A) is associated with Bardet-Biedl syndrome, Bardet-Biedl syndrome 8, retinitis pigmentosa (ClinVar).

How common is TTC8 p.Pro467= (c.1401G>A) in the general population?

TTC8 p.Pro467= (c.1401G>A) is low-frequency (popmax 1.02%, afr) (gnomAD).

How is Bardet-Biedl syndrome inherited?

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

TTC8 p.Pro467=

c.1401G>A · rs114064158 · VCV262513

Conflicting classifications of pathogenicity Conflicting submitters

Classification

Conflicting classifications of pathogenicity

ClinVar

Review

Conflicting submitters ★☆☆☆

ClinVar · 5 submitters

gnomAD v4.1

Rare

low-frequency (popmax 1.02%, afr)

Conditions

Bardet-Biedl syndrome

Computational evidence

Protein change
Missense predictors do not apply to this variant type; conservation carries the signal.
REVEL	0.077	moderately benign-leaning
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP -4.8	GERP -3.3
Overall
CADD	2.12	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 1.02% African / African-American · 767/74,886 alleles

Filtering AF 0.964% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.94%

Overall 0.0599% 966/1,612,240 alleles · low-frequency

Ancestry group	Frequency	1 in
African / African-Americangrpmax	1.02%	98
Ashkenazi Jewishnot grpmax-eligible	0.139%	721
Admixed American	0.0884%	1,131
Remaining individualsnot grpmax-eligible	0.0785%	1,274
Middle Eastern	0.0496%	2,017
East Asian	0.00671%	14,913
European (non-Finnish)	0.00407%	24,569
South Asian	0.0022%	45,481

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.Pro467=
Coding: c.1401G>A
MANE Select: NM_144596
dbSNP: rs114064158
Type: single nucleotide variant
Location: chr14:88875079 (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

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

Also linked: Bardet-Biedl syndrome 8 retinitis pigmentosa

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.Pro467Leu Uncertain significance ★★ same residue
TTC8 p.Pro467Ser 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

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-pro467 (accessed [today's date]).

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