Is SMS p.Arg268= (c.804A>G) pathogenic?

SMS p.Arg268= (c.804A>G) is classified Likely benign in SMS (ClinVar, Single submitter, 1 submitter; last evaluated 2020-01-22). Absent from gnomAD v4.1; Associated with Inborn genetic diseases.

What condition is associated with SMS p.Arg268= (c.804A>G)?

SMS p.Arg268= (c.804A>G) is associated with Inborn genetic diseases (ClinVar).

How common is SMS p.Arg268= (c.804A>G) in the general population?

SMS p.Arg268= (c.804A>G) is absent from gnomAD v4.1 (gnomAD).

SMS p.Arg268=

c.804A>G · rs2519678143 · VCV1761783

Likely benign Single submitter

Classification

Likely benign

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

gnomAD v4.1

Absent

absent from gnomAD v4.1

Conditions

Inborn genetic diseases

Computational evidence

Protein change
Missense predictors do not apply to this variant type; conservation/SpliceAI carries the signal.
Splicing
SpliceAI	Δ0.26	donor gain · deltas
Constraint at this position
Conservation	phyloP 5.1	GERP -0.57, phastCons 1
Overall
CADD	16.07	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Absent from gnomAD v4.1. Not observed in any sequenced alleles — a rarity signal (ACMG PM2-supporting), not evidence of pathogenicity on its own.

Variant & gene context

Gene: SMS
Protein: p.Arg268=
Coding: c.804A>G
MANE Select: NM_004595
dbSNP: rs2519678143
Type: single nucleotide variant
Location: chrX:21984357 (GRCh38)
Structure: AlphaFold pLDDT 95.09 · 2 PDB
Residue 268: 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.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.Glu187= Benign/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-arg268 (accessed [today's date]).

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