Is TTC8 p.Lys95Arg (c.284A>G) pathogenic?

TTC8 p.Lys95Arg (c.284A>G) is classified Conflicting classifications of pathogenicity in TTC8 (ClinVar, Conflicting submitters, 11 submitters; last evaluated 2026-06-01). Low-frequency (popmax 2.34%, sas); Associated with retinitis pigmentosa.

What condition is associated with TTC8 p.Lys95Arg (c.284A>G)?

TTC8 p.Lys95Arg (c.284A>G) is associated with retinitis pigmentosa, Bardet-Biedl syndrome 8, Bardet-Biedl syndrome (ClinVar).

How common is TTC8 p.Lys95Arg (c.284A>G) in the general population?

TTC8 p.Lys95Arg (c.284A>G) is low-frequency (popmax 2.34%, sas) (gnomAD).

How is Retinitis pigmentosa inherited?

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

TTC8 p.Lys95Arg

c.284A>G · rs150880478 · VCV196600

Conflicting classifications of pathogenicity Conflicting submitters

Classification

Conflicting classifications of pathogenicity

ClinVar

Review

Conflicting submitters ★☆☆☆

ClinVar · 11 submitters

gnomAD v4.1

Rare

low-frequency (popmax 2.34%, sas)

Conditions

retinitis pigmentosa

Computational evidence

Protein change
Missense predictors do not apply to this variant type; conservation carries the signal.
REVEL	0.349	indeterminate
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 9.3	GERP 1.3, phastCons 1
Regional constraint	o/e 0.98	unconstrained · MANE · 53 kb · p 0.62 · regional, not allelic
Overall
CADD	18.98	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 2.34% South Asian · 2,127/91,080 alleles

Filtering AF 2.25% ClinGen BA1/BS1 input FAF95, joint · FAF99 2.22%

Overall 0.454% 7,333/1,614,074 alleles · low-frequency exomes 6,799/1,461,758 · genomes 534/152,316 · joint denominator

Ancestry group	Frequency	1 in
South Asiangrpmax	2.34%	43
Middle Eastern	1.8%	56
Remaining individualsnot grpmax-eligible	0.501%	200
European (non-Finnish)	0.377%	265
Admixed American	0.368%	271
Ashkenazi Jewishnot grpmax-eligible	0.0912%	1,097
African / African-American	0.0613%	1,631
Finnishnot grpmax-eligible	0.0578%	1,731

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.Lys95Arg
Coding: c.284A>G
MANE Select: NM_144596
dbSNP: rs150880478
Type: single nucleotide variant
Location: chr14:88840883 (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 — 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-p-lys95arg (accessed [today's date]).

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