Is TTC8 p.Lys223= (c.669G>A) pathogenic?

TTC8 p.Lys223= (c.669G>A) is classified Conflicting classifications of pathogenicity in TTC8 (ClinVar, Conflicting submitters, 7 submitters; last evaluated 2026-01-21). Rare (popmax 0.412%, sas); Associated with retinitis pigmentosa.

What condition is associated with TTC8 p.Lys223= (c.669G>A)?

TTC8 p.Lys223= (c.669G>A) is associated with retinitis pigmentosa, Bardet-Biedl syndrome 8, Bardet-Biedl syndrome (ClinVar).

How common is TTC8 p.Lys223= (c.669G>A) in the general population?

TTC8 p.Lys223= (c.669G>A) is rare (popmax 0.412%, 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.Lys223=

c.669G>A · rs141304350 · VCV262517

Conflicting classifications of pathogenicity Conflicting submitters

Classification

Conflicting classifications of pathogenicity

ClinVar

Review

Conflicting submitters ★☆☆☆

ClinVar · 7 submitters

gnomAD v4.1

Rare

rare (popmax 0.412%, sas)

Conditions

retinitis pigmentosa

Computational evidence

Protein change
Missense predictors do not apply to this variant type; conservation carries the signal.
REVEL	0.071	moderately benign-leaning
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 5.2	GERP 1.7, phastCons 1
Overall
CADD	8.912	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.412% South Asian · 375/91,078 alleles

Filtering AF 0.377% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.364%

Overall 0.0584% 942/1,613,556 alleles · rare

Ancestry group	Frequency	1 in
South Asiangrpmax	0.412%	243
Middle Eastern	0.132%	757
Ashkenazi Jewishnot grpmax-eligible	0.0676%	1,479
Remaining individualsnot grpmax-eligible	0.0496%	2,015
European (non-Finnish)	0.041%	2,437
Finnishnot grpmax-eligible	0.025%	4,000
Admixed American	0.00667%	14,993
African / African-American	0.00533%	18,756

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.Lys223=
Coding: c.669G>A
MANE Select: NM_144596
dbSNP: rs141304350
Type: single nucleotide variant
Location: chr14:88853015 (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-lys223 (accessed [today's date]).

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