Is SMARCA2 p.Asp618= (c.1854C>T) pathogenic?

SMARCA2 p.Asp618= (c.1854C>T) is classified Conflicting classifications of pathogenicity in SMARCA2 (ClinVar, Conflicting submitters, 6 submitters; last evaluated 2026-01-28). Ultra-rare (popmax 0.0468%, eas); Associated with Inborn genetic diseases.

What condition is associated with SMARCA2 p.Asp618= (c.1854C>T)?

SMARCA2 p.Asp618= (c.1854C>T) is associated with Inborn genetic diseases, intellectual disability-sparse hair-brachydactyly syndrome (ClinVar).

How common is SMARCA2 p.Asp618= (c.1854C>T) in the general population?

SMARCA2 p.Asp618= (c.1854C>T) is ultra-rare (popmax 0.0468%, eas) (gnomAD).

SMARCA2 p.Asp618=

c.1854C>T · rs140464170 · VCV212224

Conflicting classifications of pathogenicity Conflicting submitters

Classification

Conflicting classifications of pathogenicity

ClinVar

Review

Conflicting submitters ★☆☆☆

ClinVar · 6 submitters

gnomAD v4.1

Rare

ultra-rare (popmax 0.0468%, eas)

Conditions

Inborn genetic diseases

Computational evidence

Protein change
Missense predictors do not apply to this variant type; conservation carries the signal.
Splicing
SpliceAI	<0.2	no splice effect predicted · four deltas, not one · how we know
Constraint at this position
Conservation	phyloP -13	GERP -5.4
Overall
CADD	0.946	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.0468% East Asian · 21/44,896 alleles

Filtering AF 0.0313% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.0262%

Overall 0.00923% 149/1,614,072 alleles · ultra-rare exomes 140/1,461,880 · genomes 9/152,192 · joint denominator

Ancestry group	Frequency	1 in
East Asiangrpmax	0.0468%	2,138
Remaining individualsnot grpmax-eligible	0.04%	2,500
South Asian	0.0209%	4,794
African / African-American	0.0107%	9,365
European (non-Finnish)	0.00619%	16,165
Finnishnot grpmax-eligible	0.00312%	32,020
Admixed American	0.00167%	60,008

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: SMARCA2
Protein: p.Asp618=
Coding: c.1854C>T
MANE Select: NM_003070
dbSNP: rs140464170
Type: single nucleotide variant
Location: chr9:2073319 (GRCh38)
Gene constraint: LOEUF 0.317 · pLI 1.00 · ClinGen HI 0/3 (gnomAD)
Structure: AlphaFold pLDDT 66.06 · 32 PDB

Full SMARCA2 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

Also linked: intellectual disability-sparse hair-brachydactyly syndrome

Similar variants

SMARCA2 p.Ala1138Pro Pathogenic/Likely pathogenic ★★ same condition
SMARCA2 p.Ala1160Gly Pathogenic ★★ same condition
SMARCA2 p.Ala1201Val Pathogenic/Likely pathogenic ★★ same condition
SMARCA2 p.Arg1105Cys Pathogenic ★★ same condition
SMARCA2 p.Arg1105His Pathogenic ★★ same condition
SMARCA2 p.Arg1105Pro Pathogenic/Likely pathogenic ★★ same condition
SMARCA2 p.Arg1159Gln Pathogenic/Likely pathogenic ★★ same condition
SMARCA2 p.Arg1159Gly 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/smarca2-p-asp618 (accessed [today's date]).

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