Is TTC8 p.Ala488Val (c.1463C>T) pathogenic?

TTC8 p.Ala488Val (c.1463C>T) is classified Conflicting classifications of pathogenicity in TTC8 (ClinVar, Conflicting submitters, 8 submitters; last evaluated 2026-01-16). Rare (popmax 0.121%, eas); Associated with retinitis pigmentosa 51.

What condition is associated with TTC8 p.Ala488Val (c.1463C>T)?

TTC8 p.Ala488Val (c.1463C>T) is associated with retinitis pigmentosa 51, Bardet-Biedl syndrome 8, Bardet-Biedl syndrome (ClinVar).

How common is TTC8 p.Ala488Val (c.1463C>T) in the general population?

TTC8 p.Ala488Val (c.1463C>T) is rare (popmax 0.121%, eas) (gnomAD).

How is Retinitis pigmentosa inherited?

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

TTC8 p.Ala488Val

c.1463C>T · rs199649536 · VCV314804

Conflicting classifications of pathogenicity Conflicting submitters

Classification

Conflicting classifications of pathogenicity

ClinVar

Review

Conflicting submitters ★☆☆☆

ClinVar · 8 submitters

gnomAD v4.1

Rare

rare (popmax 0.121%, eas)

Conditions

retinitis pigmentosa 51

Computational evidence

Protein change
Missense predictors do not apply to this variant type; conservation carries the signal.
REVEL	0.257	benign-leaning
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 6	GERP 1.1, phastCons 1
Regional constraint	o/e 0.98	unconstrained · MANE · 53 kb · p 0.62 · regional, not allelic
Overall
CADD	19.68	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.121% East Asian · 54/44,794 alleles

Filtering AF 0.0948% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.0856%

Overall 0.016% 258/1,613,600 alleles · rare exomes 233/1,461,444 · genomes 25/152,156 · joint denominator

Ancestry group	Frequency	1 in
East Asiangrpmax	0.121%	830
Finnishnot grpmax-eligible	0.0281%	3,554
Remaining individualsnot grpmax-eligible	0.0208%	4,806
European (non-Finnish)	0.0138%	7,238
Admixed American	0.0117%	8,567
African / African-American	0.004%	24,993

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.Ala488Val
Coding: c.1463C>T
MANE Select: NM_144596
dbSNP: rs199649536
Type: single nucleotide variant
Location: chr14:88877325 (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

retinitis pigmentosa 51 — disease report on Sugi Atlas → Associated genes, phenotypes, clinical trials & treatments

Also linked: Bardet-Biedl syndrome 8 Bardet-Biedl syndrome inherited retinal dystrophy retinitis pigmentosa

For Retinitis pigmentosa (Orphanet):

Inheritance: Autosomal dominant, Autosomal recessive, Mitochondrial inheritance
Onset: Adolescent, Adult, Childhood
Prevalence: 1-5 / 10 000 (Europe)

Similar variants

TTC8 p.Ala488= Likely benign ★★ 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-ala488val (accessed [today's date]).

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