Is SPATA7 p.Val438= (c.1314A>G) pathogenic?

SPATA7 p.Val438= (c.1314A>G) is classified Likely benign in SPATA7 (ClinVar, Multiple submitters, 2 submitters; last evaluated 2025-10-06). Very rare (popmax 0.0011%, nfe); Associated with Leber congenital amaurosis 3.

What condition is associated with SPATA7 p.Val438= (c.1314A>G)?

SPATA7 p.Val438= (c.1314A>G) is associated with Leber congenital amaurosis 3 (ClinVar).

How common is SPATA7 p.Val438= (c.1314A>G) in the general population?

SPATA7 p.Val438= (c.1314A>G) is very rare (popmax 0.0011%, 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.Val438=

c.1314A>G · rs751808667 · VCV1158876

Likely benign Multiple submitters

Classification

Likely benign

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 2 submitters

gnomAD v4.1

Rare

very rare (popmax 0.0011%, 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	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 1.5	GERP -3.8, phastCons 0.14
Overall
CADD	1.601	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.0011% European (non-Finnish) · 13/1,179,964 alleles

Filtering AF 0.000615% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.000474%

Overall 0.000806% 13/1,613,870 alleles · very rare exomes 7/1,461,658 · genomes 6/152,212 · 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: SPATA7
Protein: p.Val438=
Coding: c.1314A>G
MANE Select: NM_018418
dbSNP: rs751808667
Type: single nucleotide variant
Location: chr14:88437936 (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

For Leber congenital amaurosis (Orphanet):

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

Similar variants

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
SPATA7 p.Lys163Ter Pathogenic ★★ same condition
SPATA7 c.1028+5A>G Uncertain significance ★★ 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-val438 (accessed [today's date]).

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