Is TTC8 p.Ala488= (c.1464G>A) pathogenic?

TTC8 p.Ala488= (c.1464G>A) is classified Likely benign in TTC8 (ClinVar, Multiple submitters, 4 submitters; last evaluated 2024-10-09). Ultra-rare (popmax 0.0428%, afr); Associated with Bardet-Biedl syndrome.

What condition is associated with TTC8 p.Ala488= (c.1464G>A)?

TTC8 p.Ala488= (c.1464G>A) is associated with Bardet-Biedl syndrome, retinitis pigmentosa 51, Bardet-Biedl syndrome 8 (ClinVar).

How common is TTC8 p.Ala488= (c.1464G>A) in the general population?

TTC8 p.Ala488= (c.1464G>A) is ultra-rare (popmax 0.0428%, 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.Ala488=

c.1464G>A · rs142073418 · VCV1627334

Likely benign Multiple submitters

Classification

Likely benign

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 4 submitters

gnomAD v4.1

Rare

ultra-rare (popmax 0.0428%, afr)

Conditions

Bardet-Biedl syndrome

Computational evidence

Protein change
Missense predictors do not apply to this variant type; conservation carries the signal.
REVEL	0.009	strongly benign-leaning
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP -0.64	GERP -3.8, phastCons 0.016
Overall
CADD	9.237	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.0428% African / African-American · 32/74,832 alleles

Filtering AF 0.031% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.0271%

Overall 0.00279% 45/1,613,404 alleles · ultra-rare exomes 28/1,461,440 · genomes 17/151,964 · joint denominator

Ancestry group	Frequency	1 in
African / African-Americangrpmax	0.0428%	2,338
Middle Eastern	0.0165%	6,078
Remaining individualsnot grpmax-eligible	0.0032%	31,229
European (non-Finnish)	0.000848%	117,976

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.Ala488=
Coding: c.1464G>A
MANE Select: NM_144596
dbSNP: rs142073418
Type: single nucleotide variant
Location: chr14:88877326 (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: retinitis pigmentosa 51 Bardet-Biedl syndrome 8

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.Ala488Val Conflicting classifications of pathogenicity ★ 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-ala488 (accessed [today's date]).

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