Is SPATA7 p.Pro353Ser (c.1057C>T) pathogenic?

SPATA7 p.Pro353Ser (c.1057C>T) is classified Uncertain significance in SPATA7 (ClinVar, Single submitter, 1 submitter; last evaluated 2022-04-08). AlphaMissense: likely benign (0.0777); Absent from gnomAD v4.1; Associated with Leber congenital amaurosis 3.

What condition is associated with SPATA7 p.Pro353Ser (c.1057C>T)?

SPATA7 p.Pro353Ser (c.1057C>T) is associated with Leber congenital amaurosis 3 (ClinVar).

How common is SPATA7 p.Pro353Ser (c.1057C>T) in the general population?

SPATA7 p.Pro353Ser (c.1057C>T) is absent from gnomAD v4.1 (gnomAD).

How is Leber congenital amaurosis inherited?

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

What do computational predictors say about SPATA7 p.Pro353Ser (c.1057C>T)?

AlphaMissense predicts likely benign (score 0.0777) — an in-silico prediction, not a clinical call.

SPATA7 p.Pro353Ser

c.1057C>T · rs2076931415 · VCV2095983

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.0777 · ACMG-weighted

gnomAD v4.1

Absent

absent from gnomAD v4.1

Missense predictors

0/3 damaging

AlphaMissense, REVEL, SaProt

Conditions

Leber congenital amaurosis 3

Computational evidence

Protein change
AlphaMissense	0.0777	likely benign
REVEL	0.017	moderately benign-leaning
SaProt	LLR -4.75	tolerated
⇒ AlphaMissense, REVEL and SaProt all call this tolerated.
Splicing
SpliceAI	<0.2	all four deltas below 0.2 · C>G here scores Δ0.25 · evaluated, not missing
Constraint at this position
Conservation	phyloP -0.067	GERP -1.7
Regional constraint	o/e 0.97	unconstrained · MANE · 53 kb · p 0.49 · regional, not allelic
Overall
CADD	2.866	PHRED · no single calibrated threshold — expert panels disagree

ClinVar classifies this uncertain; the computational predictors unanimously lean tolerated — a triage signal, not a reclassification

AlphaMissense carries the ACMG weight for missense; REVEL and SaProt are independent agreement signals.

Population frequency

gnomAD v4.1 · exomes + genomes

Absent from gnomAD v4.1. Not observed in any sequenced alleles — a rarity signal (ACMG PM2-supporting), not evidence of pathogenicity on its own.

Variant & gene context

Gene: SPATA7
Protein: p.Pro353Ser
Coding: c.1057C>T
MANE Select: NM_018418
dbSNP: rs2076931415
Type: single nucleotide variant
Location: chr14:88431200 (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 p.Pro353Ala 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
SPATA7 p.Lys163Ter 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-pro353ser (accessed [today's date]).

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