Is SPEF2 p.Arg1064= (c.3192A>G) pathogenic?

SPEF2 p.Arg1064= (c.3192A>G) is classified Likely benign in SPEF2 (ClinVar, Single submitter, 1 submitter; last evaluated 2024-09-25). Absent from gnomAD v4.1; Associated with Inborn genetic diseases.

What condition is associated with SPEF2 p.Arg1064= (c.3192A>G)?

SPEF2 p.Arg1064= (c.3192A>G) is associated with Inborn genetic diseases (ClinVar).

How common is SPEF2 p.Arg1064= (c.3192A>G) in the general population?

SPEF2 p.Arg1064= (c.3192A>G) is absent from gnomAD v4.1 (gnomAD).

SPEF2 p.Arg1064=

c.3192A>G · VCV3448337

Likely benign Single submitter

Classification

Likely benign

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

gnomAD v4.1

Absent

absent from gnomAD v4.1

Conditions

Inborn genetic diseases

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 1.7	GERP -0.78, phastCons 1
Overall
CADD	2.963	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: SPEF2
Protein: p.Arg1064=
Coding: c.3192A>G
MANE Select: NM_024867
Type: single nucleotide variant
Location: chr5:35740129 (GRCh38)
Gene constraint: LOEUF 0.923 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 71.30
Residue 1064: a UniProt-annotated variant site (in spgf43; loss of protein expression; changed sperm axoneme assembly); a UniProt-annotated variant site (found in a female patient with primary ciliary dyskinesia-like symptoms including chronic sinusitis, bronchitis, chronic wet cough and recurrent pneumonia; uncertain significance)

Full SPEF2 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Disease context

Inborn genetic diseases — disease report on Sugi Atlas → Associated genes, phenotypes, clinical trials & treatments

Similar variants

SPEF2 p.Asp797Gly Uncertain significance ★★ ⚠ same condition
SPEF2 p.Glu116Lys Uncertain significance ★★ ⚠ same condition
SPEF2 p.Glu1752Gln Uncertain significance ★★ ⚠ same condition
SPEF2 p.Ala1122Thr Uncertain significance ★ ⚠ same condition
SPEF2 p.Ala1323Val Uncertain significance ★ ⚠ same condition
SPEF2 p.Ala1355Thr Uncertain significance ★ ⚠ same condition
SPEF2 p.Ala1405Ser Uncertain significance ★ ⚠ same condition
SPEF2 p.Ala1772Thr 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/spef2-p-arg1064 (accessed [today's date]).

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