Is SMARCA2 p.Pro199= (c.597C>T) pathogenic?

SMARCA2 p.Pro199= (c.597C>T) is classified Benign/Likely benign in SMARCA2 (ClinVar, Multiple submitters, 2 submitters; last evaluated 2024-06-01). Ultra-rare (popmax 0.0176%, sas); Associated with intellectual disability-sparse hair-brachydactyly syndrome.

What condition is associated with SMARCA2 p.Pro199= (c.597C>T)?

SMARCA2 p.Pro199= (c.597C>T) is associated with intellectual disability-sparse hair-brachydactyly syndrome (ClinVar).

How common is SMARCA2 p.Pro199= (c.597C>T) in the general population?

SMARCA2 p.Pro199= (c.597C>T) is ultra-rare (popmax 0.0176%, sas) (gnomAD).

SMARCA2 p.Pro199=

c.597C>T · rs747247552 · VCV914909

Benign/Likely benign Multiple submitters

Classification

Benign/Likely benign

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 2 submitters

gnomAD v4.1

Rare

ultra-rare (popmax 0.0176%, sas)

Conditions

intellectual disability-sparse hair-brachydactyly 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 -15	GERP -5.1
Overall
CADD	1.44	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.0176% South Asian · 16/91,078 alleles

Filtering AF 0.011% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.00888%

Overall 0.00366% 59/1,613,854 alleles · ultra-rare exomes 56/1,461,666 · genomes 3/152,188 · joint denominator

Ancestry group	Frequency	1 in
South Asiangrpmax	0.0176%	5,692
Middle Eastern	0.017%	5,898
African / African-American	0.00667%	14,984
Admixed American	0.00333%	30,003
Remaining individualsnot grpmax-eligible	0.0032%	31,229
Finnishnot grpmax-eligible	0.00312%	32,022
European (non-Finnish)	0.00263%	38,066

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.Pro199=
Coding: c.597C>T
MANE Select: NM_003070
dbSNP: rs747247552
Type: single nucleotide variant
Location: chr9:2039707 (GRCh38)
Gene constraint: LOEUF 0.317 · pLI 1.00 · ClinGen HI 0/3 (gnomAD)
Structure: AlphaFold pLDDT 66.06 · 32 PDB
Residue 199: the qlq domain

Full SMARCA2 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Disease context

intellectual disability-sparse hair-brachydactyly syndrome — disease report on Sugi Atlas → Associated genes, phenotypes, clinical trials & treatments

Similar variants

SMARCA2 p.Pro199Ser Uncertain significance ★ ⚠ same residue
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-pro199 (accessed [today's date]).

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