Is SPATA7 p.Arg243= (c.729C>T) pathogenic?

SPATA7 p.Arg243= (c.729C>T) is classified Conflicting classifications of pathogenicity in SPATA7 (ClinVar, Conflicting submitters, 7 submitters; last evaluated 2026-02-01). Rare (popmax 0.348%, nfe); Associated with Leber congenital amaurosis 3.

What condition is associated with SPATA7 p.Arg243= (c.729C>T)?

SPATA7 p.Arg243= (c.729C>T) is associated with Leber congenital amaurosis 3, retinitis pigmentosa (ClinVar).

How common is SPATA7 p.Arg243= (c.729C>T) in the general population?

SPATA7 p.Arg243= (c.729C>T) is rare (popmax 0.348%, nfe) (gnomAD).

How is Leber congenital amaurosis inherited?

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

SPATA7 p.Arg243=

c.729C>T · rs151338404 · VCV95908

Conflicting classifications of pathogenicity Conflicting submitters

Classification

Conflicting classifications of pathogenicity

ClinVar

Review

Conflicting submitters ★☆☆☆

ClinVar · 7 submitters

gnomAD v4.1

Rare

rare (popmax 0.348%, nfe)

Conditions

Leber congenital amaurosis 3

Computational evidence

Protein change
Missense predictors do not apply to this variant type; conservation carries the signal.
Splicing
SpliceAI	<0.2	no splice effect predicted · four deltas, not one · how we know
Constraint at this position
Conservation	phyloP -0.11	GERP 1.3, phastCons 0.46
Overall
CADD	8.787	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.348% European (non-Finnish) · 4,104/1,180,014 alleles

Filtering AF 0.339% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.335%

Overall 0.295% 4,763/1,614,156 alleles · rare exomes 4,496/1,461,852 · genomes 267/152,304 · joint denominator

Ancestry group	Frequency	1 in
European (non-Finnish)grpmax	0.348%	288
South Asian	0.299%	335
Admixed American	0.273%	366
Remaining individualsnot grpmax-eligible	0.227%	440
Middle Eastern	0.132%	758
African / African-American	0.0573%	1,745
Finnishnot grpmax-eligible	0.0375%	2,668
Ashkenazi Jewishnot grpmax-eligible	0.0203%	4,935

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: SPATA7
Protein: p.Arg243=
Coding: c.729C>T
MANE Select: NM_018418
dbSNP: rs151338404
Type: single nucleotide variant
Location: chr14:88426588 (GRCh38)
Gene constraint: LOEUF 1.22 · pLI <0.01 · ClinGen HI gene assoc. with recessive phenotype (gnomAD)
Structure: AlphaFold pLDDT 58.28

Full SPATA7 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Disease context

Leber congenital amaurosis 3 — disease report on Sugi Atlas → Associated genes, phenotypes, clinical trials & treatments

Also linked: retinitis pigmentosa

For Leber congenital amaurosis (Orphanet):

Inheritance: Autosomal dominant, Autosomal recessive
Onset: Infancy, Neonatal
Prevalence: 1-9 / 100 000 (Europe)

Similar variants

SPATA7 p.Arg243His Uncertain significance ★★ same residue
SPATA7 p.Arg243Cys Uncertain significance ★ same residue
SPATA7 c.94+2T>C Likely pathogenic ★★ same condition
SPATA7 p.Arg108Ter Pathogenic/Likely pathogenic ★★ same condition
SPATA7 p.Arg391Ter Pathogenic/Likely pathogenic ★★ same condition
SPATA7 p.Arg395Ter Pathogenic/Likely pathogenic ★★ same condition
SPATA7 p.Arg85Ter Pathogenic/Likely pathogenic ★★ same condition
SPATA7 p.Cys96Ter 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/spata7-p-arg243 (accessed [today's date]).

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