Is SMARCA2 p.Pro173Ser (c.517C>T) pathogenic?

SMARCA2 p.Pro173Ser (c.517C>T) is classified Benign in SMARCA2 (ClinVar, Single submitter, 1 submitter; last evaluated 2018-01-12). AlphaMissense: likely benign (0.1237); Rare (popmax 0.11%, sas); Associated with intellectual disability-sparse hair-brachydactyly syndrome.

What condition is associated with SMARCA2 p.Pro173Ser (c.517C>T)?

SMARCA2 p.Pro173Ser (c.517C>T) is associated with intellectual disability-sparse hair-brachydactyly syndrome (ClinVar).

How common is SMARCA2 p.Pro173Ser (c.517C>T) in the general population?

SMARCA2 p.Pro173Ser (c.517C>T) is rare (popmax 0.11%, sas) (gnomAD).

What do computational predictors say about SMARCA2 p.Pro173Ser (c.517C>T)?

AlphaMissense predicts likely benign (score 0.1237) — an in-silico prediction, not a clinical call.

SMARCA2 p.Pro173Ser

c.517C>T · rs768229159 · VCV914908

Benign Single submitter

Classification

Benign

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.1237 · ACMG-weighted

gnomAD v4.1

Rare

rare (popmax 0.11%, sas)

Missense predictors

0/2 damaging

AlphaMissense, SaProt · REVEL indeterminate

Conditions

intellectual disability-sparse hair-brachydactyly syndrome

Computational evidence

Protein change
AlphaMissense	0.1237	likely benign
REVEL	0.382	indeterminate
SaProt	LLR -7.03	tolerated
⇒ AlphaMissense and SaProt both call this tolerated; REVEL is indeterminate.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 7.7	GERP 1.6, phastCons 1
Regional constraint	o/e 1.11	unconstrained · MANE · 11 kb · p 0.08 · regional, not allelic
Overall
CADD	22.4	PHRED · no single calibrated threshold — expert panels disagree

AlphaMissense carries the ACMG weight for missense; REVEL and SaProt are independent agreement signals.

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.11% South Asian · 100/91,088 alleles

Filtering AF 0.0923% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.0858%

Overall 0.00669% 108/1,614,220 alleles · rare exomes 105/1,461,894 · genomes 3/152,326 · joint denominator

Ancestry group	Frequency	1 in
South Asiangrpmax	0.11%	911
Middle Eastern	0.0165%	6,062
Admixed American	0.005%	20,010
Remaining individualsnot grpmax-eligible	0.0048%	20,836
European (non-Finnish)	8.47e-05%	1,180,050

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.Pro173Ser
Coding: c.517C>T
MANE Select: NM_003070
dbSNP: rs768229159
Type: single nucleotide variant
Location: chr9:2039627 (GRCh38)
Gene constraint: LOEUF 0.317 · pLI 1.00 · ClinGen HI 0/3 (gnomAD)
Structure: AlphaFold pLDDT 66.06 · 32 PDB
Residue 173: the qlq domain; the 'disordered' region

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.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
SMARCA2 p.Arg1162Cys Pathogenic/Likely 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-pro173ser (accessed [today's date]).

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