Is SMARCD1 p.Arg503= (c.1507C>A) pathogenic?

SMARCD1 p.Arg503= (c.1507C>A) is classified Likely benign in SMARCD1 (ClinVar, Single submitter, 1 submitter; last evaluated 2022-10-28). Very rare (popmax 0.00167%, amr).

How common is SMARCD1 p.Arg503= (c.1507C>A) in the general population?

SMARCD1 p.Arg503= (c.1507C>A) is very rare (popmax 0.00167%, amr) (gnomAD).

SMARCD1 p.Arg503=

c.1507C>A · VCV4916753

Likely benign Single submitter

Classification

Likely benign

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

gnomAD v4.1

Rare

very rare (popmax 0.00167%, amr)

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	GERP 0.87, phastCons 1
Overall
CADD	11.26	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.00167% Admixed American · 1/60,004 alleles

Filtering AF 6.8e-05% ClinGen BA1/BS1 input FAF95, joint · FAF99 1.9e-05%

Overall 0.000248% 4/1,613,976 alleles · very rare exomes 2/1,461,822 · genomes 2/152,154 · joint denominator

Ancestry group	Frequency	1 in
Admixed Americangrpmax	0.00167%	60,004
European (non-Finnish)	0.000254%	393,326

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: SMARCD1
Protein: p.Arg503=
Coding: c.1507C>A
MANE Select: NM_003076
Type: single nucleotide variant
Location: chr12:50098959 (GRCh38)
Gene constraint: LOEUF 0.339 · pLI 1.00 (gnomAD)
Structure: AlphaFold pLDDT 78.37 · 12 PDB
Residue 503: a UniProt-annotated variant site (in css11; does not affect the interaction with smarcc1 and smarca4); a UniProt-annotated variant site (in css11); an α-helix; the 'necessary for gr/nr3c1-mediated remodeling and transcription from chromatin; required for gr/nr3c1 interaction with the brg1/smarca4 complex in vivo' region

Full SMARCD1 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Similar variants

SMARCD1 p.Arg503Ter Pathogenic ★ same residue
SMARCD1 p.Arg503del Uncertain significance ★ same residue
SMARCD1 p.Ala302Gly Uncertain significance ★★ same type
SMARCD1 p.Arg334Gln Uncertain significance ★★ ⚠ same type
SMARCD1 p.Asp247Gly Uncertain significance ★★ ⚠ same type
SMARCD1 p.Ile184Val Uncertain significance ★★ ⚠ same type
SMARCD1 p.Ile323Val Uncertain significance ★★ ⚠ same type
SMARCD1 p.Thr189Ser Uncertain significance ★★ ⚠ same type

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/smarcd1-p-arg503 (accessed [today's date]).

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