Is SPAG1 p.Arg76= (c.228G>A) pathogenic?

SPAG1 p.Arg76= (c.228G>A) is classified Likely benign in SPAG1 (ClinVar, Single submitter, 1 submitter; last evaluated 2024-05-06). Absent from gnomAD v4.1; Associated with primary ciliary dyskinesia 28.

What condition is associated with SPAG1 p.Arg76= (c.228G>A)?

SPAG1 p.Arg76= (c.228G>A) is associated with primary ciliary dyskinesia 28 (ClinVar).

How common is SPAG1 p.Arg76= (c.228G>A) in the general population?

SPAG1 p.Arg76= (c.228G>A) is absent from gnomAD v4.1 (gnomAD).

How is Primary ciliary dyskinesia inherited?

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

SPAG1 p.Arg76=

c.228G>A · VCV3652452

Likely benign Single submitter

Classification

Likely benign

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

gnomAD v4.1

Absent

absent from gnomAD v4.1

Conditions

primary ciliary dyskinesia 28

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 4.4	GERP 0.86, phastCons 1
Overall
CADD	10.71	PHRED · no single calibrated threshold — expert panels disagree

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: SPAG1
Protein: p.Arg76=
Coding: c.228G>A
MANE Select: NM_003114
Type: single nucleotide variant
Location: chr8:100165901 (GRCh38)
Gene constraint: LOEUF 1.084 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 74.50 · 4 PDB

Full SPAG1 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Disease context

primary ciliary dyskinesia 28 — disease report on Sugi Atlas → Associated genes, phenotypes, clinical trials & treatments

For Primary ciliary dyskinesia (Orphanet):

Inheritance: Autosomal dominant, Autosomal recessive, X-linked recessive
Onset: Neonatal
Prevalence: 1-5 / 10 000 (Pakistan)

Similar variants

SPAG1 c.1097-11C>G Pathogenic ★★ same condition
SPAG1 c.939+1G>A Likely pathogenic ★★ same condition
SPAG1 p.Arg697Ter Pathogenic ★★ same condition
SPAG1 p.Gln672Ter Pathogenic/Likely pathogenic ★★ same condition
SPAG1 p.Ala159Thr Uncertain significance ★★ ⚠ same condition
SPAG1 p.Ala159Val Uncertain significance ★★ ⚠ same condition
SPAG1 p.Ala642Thr Uncertain significance ★★ ⚠ same condition
SPAG1 p.Arg132His 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/spag1-p-arg76 (accessed [today's date]).

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