Is SPRED1 p.Pro177= (c.531C>G) pathogenic?

SPRED1 p.Pro177= (c.531C>G) is classified Likely benign in SPRED1 (ClinVar, Single submitter, 1 submitter; last evaluated 2023-07-19). Absent from gnomAD v4.1; Associated with Legius syndrome.

What condition is associated with SPRED1 p.Pro177= (c.531C>G)?

SPRED1 p.Pro177= (c.531C>G) is associated with Legius syndrome (ClinVar).

How common is SPRED1 p.Pro177= (c.531C>G) in the general population?

SPRED1 p.Pro177= (c.531C>G) is absent from gnomAD v4.1 (gnomAD).

SPRED1 p.Pro177=

c.531C>G · rs1595756882 · VCV2900459

Likely benign Single submitter

Classification

Likely benign

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

gnomAD v4.1

Absent

absent from gnomAD v4.1

Conditions

Legius syndrome

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 -1.1	GERP -1.2, phastCons 0.001
Overall
CADD	8.316	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: SPRED1
Protein: p.Pro177=
Coding: c.531C>G
MANE Select: NM_152594
dbSNP: rs1595756882
Type: single nucleotide variant
Location: chr15:38339844 (GRCh38)
Gene constraint: LOEUF 0.496 · pLI 0.98 · ClinGen HI 3/3 (gnomAD)
Structure: AlphaFold pLDDT 63.67 · 3 PDB

Full SPRED1 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Disease context

Legius syndrome — disease report on Sugi Atlas → Associated genes, phenotypes, clinical trials & treatments

Similar variants

SPRED1 p.Pro177Leu Uncertain significance ★ ⚠ same residue
SPRED1 p.Pro177Arg Uncertain significance ★ ⚠ same residue
SPRED1 p.Pro177Ser Uncertain significance ★ ⚠ same residue
SPRED1 p.Arg117Ter Pathogenic ★★ same condition
SPRED1 p.Arg16Ter Pathogenic ★★ same condition
SPRED1 p.Arg18Ter Pathogenic ★★ same condition
SPRED1 p.Arg24Ter Pathogenic ★★ same condition
SPRED1 p.Arg251Ter Pathogenic/Likely 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/spred1-p-pro177 (accessed [today's date]).

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