Is SMS p.Glu187= (c.561A>G) pathogenic?

SMS p.Glu187= (c.561A>G) is classified Benign/Likely benign in SMS (ClinVar, Multiple submitters, 4 submitters; last evaluated 2026-02-01). Rare (popmax 0.321%, afr); Associated with Inborn genetic diseases.

What condition is associated with SMS p.Glu187= (c.561A>G)?

SMS p.Glu187= (c.561A>G) is associated with Inborn genetic diseases (ClinVar).

How common is SMS p.Glu187= (c.561A>G) in the general population?

SMS p.Glu187= (c.561A>G) is rare (popmax 0.321%, afr) (gnomAD).

SMS p.Glu187=

c.561A>G · rs138516691 · VCV590234

Benign/Likely benign Multiple submitters

Classification

Benign/Likely benign

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 4 submitters

gnomAD v4.1

Rare

rare (popmax 0.321%, afr)

Conditions

Inborn genetic diseases

Computational evidence

Protein change
Missense predictors do not apply to this variant type; conservation carries the signal.
REVEL	0.069	moderately benign-leaning
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 6.7	GERP -0.11, phastCons 1
Overall
CADD	9.136	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.321% African / African-American · 183/57,093 alleles

Filtering AF 0.282% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.268%

Overall 0.0195% 235/1,206,403 alleles · rare

Ancestry group	Frequency	1 in
African / African-Americangrpmax	0.321%	312
Admixed American	0.0612%	1,633
Remaining individualsnot grpmax-eligible	0.0358%	2,794
European (non-Finnish)	0.000785%	127,420

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: SMS
Protein: p.Glu187=
Coding: c.561A>G
MANE Select: NM_004595
dbSNP: rs138516691
Type: single nucleotide variant
Location: chrX:21978015 (GRCh38)
Structure: AlphaFold pLDDT 95.09 · 2 PDB
Residue 187: the pabs domain

Full SMS 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

Similar variants

SMS p.Glu187Asp Uncertain significance ★ ⚠ same residue
SMS p.Arg234Ter Pathogenic/Likely pathogenic ★★ same condition
SMS p.Gly56Ser Pathogenic ★★ ⚠ same condition
SMS p.Pro112Leu Pathogenic/Likely pathogenic ★★ ⚠ same condition
SMS p.Lys245Asn Uncertain significance ★★ ⚠ same condition
SMS p.Ser184Asn Uncertain significance ★★ ⚠ same condition
SMS p.Ala36Val Likely benign ★★ same condition
SMS p.Pro281= Benign/Likely benign ★★ 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/sms-p-glu187 (accessed [today's date]).

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