Is SMARCAL1 p.Asp517= (c.1551C>T) pathogenic?

SMARCAL1 p.Asp517= (c.1551C>T) is classified Likely benign in SMARCAL1 (ClinVar, Single submitter, 1 submitter; last evaluated 2025-10-24). Very rare (popmax 8.47e-05%, nfe); Associated with Schimke immuno-osseous dysplasia.

What condition is associated with SMARCAL1 p.Asp517= (c.1551C>T)?

SMARCAL1 p.Asp517= (c.1551C>T) is associated with Schimke immuno-osseous dysplasia (ClinVar).

How common is SMARCAL1 p.Asp517= (c.1551C>T) in the general population?

SMARCAL1 p.Asp517= (c.1551C>T) is very rare (popmax 8.47e-05%, nfe) (gnomAD).

How is Schimke immuno-osseous dysplasia inherited?

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

SMARCAL1 p.Asp517=

c.1551C>T · VCV4707193

Likely benign Single submitter

Classification

Likely benign

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

gnomAD v4.1

Rare

very rare (popmax 8.47e-05%, nfe)

Conditions

Schimke immuno-osseous dysplasia

Computational evidence

Protein change
Missense predictors do not apply to this variant type; conservation carries the signal.
REVEL	0.117	moderately benign-leaning
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 0.8	GERP -0.56, phastCons 0.24
Overall
CADD	6.084	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 8.47e-05% European (non-Finnish) · 1/1,180,012 alleles

Overall 6.2e-05% 1/1,614,170 alleles · very rare exomes 1/1,461,860 · genomes 0/152,310 · joint denominator

Rarity supports pathogenicity (ACMG PM2); frequency above a disease-specific BA1/BS1 threshold argues against it. A variant frequent in one ancestry group can be near-absent in others, so a single global figure can mislead.

Variant & gene context

Gene: SMARCAL1
Protein: p.Asp517=
Coding: c.1551C>T
MANE Select: NM_014140
Type: single nucleotide variant
Location: chr2:216435403 (GRCh38)
Gene constraint: LOEUF 0.795 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 70.51 · 1 PDB
Residue 517: the helicase atp-binding domain

Full SMARCAL1 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Disease context

Schimke immuno-osseous dysplasia — disease report on Sugi Atlas → Associated genes, phenotypes, clinical trials & treatments

For Schimke immuno-osseous dysplasia (Orphanet):

Inheritance: Autosomal recessive
Onset: Antenatal, Infancy, Neonatal

Similar variants

SMARCAL1 p.Asp517Gly Uncertain significance ★ ⚠ same residue
SMARCAL1 c.1334+1G>A Pathogenic/Likely pathogenic ★★ same condition
SMARCAL1 c.1485+1G>A Likely pathogenic ★★ same condition
SMARCAL1 c.1710+2T>C Likely pathogenic ★★ same condition
SMARCAL1 c.2427+1G>A Likely pathogenic ★★ same condition
SMARCAL1 c.2528+1G>A Pathogenic ★★ same condition
SMARCAL1 c.862+1G>A Likely pathogenic ★★ same condition
SMARCAL1 c.863-2A>G 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/smarcal1-p-asp517 (accessed [today's date]).

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