Is SMARCD2 p.Val515= (c.1545G>A) pathogenic?

SMARCD2 p.Val515= (c.1545G>A) is classified Benign/Likely benign in SMARCD2 (ClinVar, Multiple submitters, 7 submitters; last evaluated 2026-02-03). Rare (popmax 0.502%, nfe); Associated with specific granule deficiency 2.

What condition is associated with SMARCD2 p.Val515= (c.1545G>A)?

SMARCD2 p.Val515= (c.1545G>A) is associated with specific granule deficiency 2 (ClinVar).

How common is SMARCD2 p.Val515= (c.1545G>A) in the general population?

SMARCD2 p.Val515= (c.1545G>A) is rare (popmax 0.502%, nfe) (gnomAD).

SMARCD2 p.Val515=

Q: How is Recurrent infections due to specific granule deficiency inherited?

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

c.1545G>A · rs181910740 · VCV790464

Benign/Likely benign Multiple submitters

Classification

Benign/Likely benign

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 7 submitters

gnomAD v4.1

Rare

rare (popmax 0.502%, nfe)

Conditions

specific granule deficiency 2

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 1.4	GERP 1.4, phastCons 1
Overall
CADD	12.81	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.502% European (non-Finnish) · 5,859/1,167,658 alleles

Filtering AF 0.491% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.487%

Overall 0.438% 6,944/1,586,544 alleles · rare exomes 6,529/1,434,228 · genomes 415/152,316 · joint denominator

Ancestry group	Frequency	1 in
Finnishnot grpmax-eligible	0.516%	194
European (non-Finnish)grpmax	0.502%	199
South Asian	0.398%	251
Remaining individualsnot grpmax-eligible	0.342%	293
Middle Eastern	0.312%	320
Ashkenazi Jewishnot grpmax-eligible	0.19%	528
Admixed American	0.149%	671
African / African-American	0.074%	1,351
East Asian	0.0023%	43,454

Finnish shows a higher raw frequency than the grpmax group above it. gnomAD excludes bottlenecked groups — Finnish, Ashkenazi Jewish, Amish and “Remaining individuals” — from grpmax, because founder effects make their frequencies unrepresentative for filtering. The table is sorted by frequency, so an excluded group can sit above the grpmax row.

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: SMARCD2
Protein: p.Val515=
Coding: c.1545G>A
MANE Select: NM_001098426
dbSNP: rs181910740
Type: single nucleotide variant
Location: chr17:63832989 (GRCh38)
Gene constraint: LOEUF 0.762 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 78.38

Full SMARCD2 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Disease context

specific granule deficiency 2 — disease report on Sugi Atlas → Associated genes, phenotypes, clinical trials & treatments

For Recurrent infections due to specific granule deficiency (Orphanet):

Inheritance: Autosomal recessive
Onset: Infancy, Neonatal

Similar variants

SMARCD2 p.Arg192Ter Pathogenic/Likely pathogenic ★★ same condition
SMARCD2 c.922-3C>T Uncertain significance ★★ same condition
SMARCD2 c.568-1G>C Likely pathogenic ★ same condition
SMARCD2 p.Gln131Ter Likely pathogenic ★ same condition
SMARCD2 p.Arg477Ter Conflicting classifications of pathogenicity ★ same condition
SMARCD2 c.1181+1G>A Pathogenic same condition
SMARCD2 c.401+2T>C Pathogenic same condition
SMARCD2 p.Gln171Ter 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/smarcd2-p-val515 (accessed [today's date]).

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