Is TTC8 c.710+4A>C pathogenic?

TTC8 c.710+4A>C is classified Uncertain significance in TTC8 (ClinVar, Multiple submitters, 2 submitters; last evaluated 2024-10-26). Very rare (popmax 0.00017%, nfe); Associated with retinitis pigmentosa 51.

What condition is associated with TTC8 c.710+4A>C?

TTC8 c.710+4A>C is associated with retinitis pigmentosa 51, Bardet-Biedl syndrome 8, Bardet-Biedl syndrome (ClinVar).

How common is TTC8 c.710+4A>C in the general population?

TTC8 c.710+4A>C is very rare (popmax 0.00017%, nfe) (gnomAD).

How is Retinitis pigmentosa inherited?

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

TTC8 c.710+4A>C

rs1352481954 · VCV1480258

Uncertain significance Multiple submitters

Classification

Uncertain significance

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 2 submitters

gnomAD v4.1

Rare

very rare (popmax 0.00017%, nfe)

Conditions

retinitis pigmentosa 51

Computational evidence

Protein change
Missense predictors do not apply to this variant type; conservation carries the signal.
Splicing
Splice region	donor +4	donor splice region (+4, within the first 6 intronic nt) · inside the BP7-excluded zone
SpliceAI	<0.2	no splice effect predicted · four deltas, not one · how we know
Constraint at this position
Conservation	phyloP 6.1	GERP 1.7, phastCons 1
Non-coding constraint	Z -0.39	1 kb window · o/e 1.03 · regional · uncalibrated
Overall
CADD	16.8	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.00017% European (non-Finnish) · 2/1,176,280 alleles

Filtering AF 2.8e-05% ClinGen BA1/BS1 input FAF95, joint · FAF99 1.1e-05%

Overall 0.000124% 2/1,609,616 alleles · very rare exomes 2/1,457,336 · genomes 0/152,280 · 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
Coding: c.710+4A>C
MANE Select: NM_144596
dbSNP: rs1352481954
Type: single nucleotide variant
Location: chr14:88853060 (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

For Retinitis pigmentosa (Orphanet):

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

Similar variants

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
TTC8 p.Trp226Ter 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-c-710-plus-4a-c (accessed [today's date]).

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