Is SPATA7 p.Lys124Arg (c.371A>G) pathogenic?

SPATA7 p.Lys124Arg (c.371A>G) is classified Uncertain significance in SPATA7 (ClinVar, Single submitter, 1 submitter; last evaluated 2022-05-20). AlphaMissense: likely benign (0.1256); No allele count reported in gnomAD v4.1 (AN 1,582,300); Associated with Leber congenital amaurosis 3.

What condition is associated with SPATA7 p.Lys124Arg (c.371A>G)?

SPATA7 p.Lys124Arg (c.371A>G) is associated with Leber congenital amaurosis 3 (ClinVar).

How common is SPATA7 p.Lys124Arg (c.371A>G) in the general population?

SPATA7 p.Lys124Arg (c.371A>G) is no allele count reported in gnomAD v4.1 (AN 1,582,300) (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.Lys124Arg (c.371A>G)?

AlphaMissense predicts likely benign (score 0.1256) — an in-silico prediction, not a clinical call.

SPATA7 p.Lys124Arg

c.371A>G · rs2504193186 · VCV2125678

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.1256 · ACMG-weighted

gnomAD v4.1

Not reported

no allele count reported in gnomAD v4.1 (AN 1,582,300)

Missense predictors

0/3 damaging

AlphaMissense, REVEL, SaProt

Conditions

Leber congenital amaurosis 3

Computational evidence

Protein change
AlphaMissense	0.1256	likely benign
REVEL	0.04	moderately benign-leaning
SaProt	LLR -6.39	tolerated
⇒ AlphaMissense, REVEL and SaProt all call this tolerated.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 6.9	GERP 0.53, phastCons 1
Regional constraint	o/e 0.97	unconstrained · MANE · 53 kb · p 0.49 · regional, not allelic
Overall
CADD	22.9	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

No allele count reported in gnomAD v4.1 (AN 1,582,300). This is missing data, not an absence: the variant may or may not be present in gnomAD. Rarity (ACMG PM2) and BA1/BS1 cannot be assessed for it.

Variant & gene context

Gene: SPATA7
Protein: p.Lys124Arg
Coding: c.371A>G
MANE Select: NM_018418
dbSNP: rs2504193186
Type: single nucleotide variant
Location: chr14:88416843 (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-lys124arg (accessed [today's date]).

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