Is SMS p.Glu340= (c.1020A>G) pathogenic?

SMS p.Glu340= (c.1020A>G) is classified Likely benign in SMS (ClinVar, No assertion criteria, 1 submitter; last evaluated 2019-04-09). Very rare (popmax 0.00883%, sas); Associated with SMS-related disorder.

What condition is associated with SMS p.Glu340= (c.1020A>G)?

SMS p.Glu340= (c.1020A>G) is associated with SMS-related disorder (ClinVar).

How common is SMS p.Glu340= (c.1020A>G) in the general population?

SMS p.Glu340= (c.1020A>G) is very rare (popmax 0.00883%, sas) (gnomAD).

SMS p.Glu340=

c.1020A>G · rs754800675 · VCV3047524

Likely benign No assertion criteria

Classification

Likely benign

ClinVar

Review

No assertion criteria ☆☆☆☆

ClinVar · 1 submitter

gnomAD v4.1

Rare

very rare (popmax 0.00883%, sas)

Conditions

SMS-related disorder

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 1.5	GERP 1.1, phastCons 1
Overall
CADD	5.415	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.00883% South Asian · 5/56,633 alleles

Filtering AF 0.00341% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.00217%

Overall 0.000417% 5/1,199,209 alleles · very rare exomes 5/1,085,584 · genomes 0/113,625 · joint denominator

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.Glu340=
Coding: c.1020A>G
MANE Select: NM_004595
dbSNP: rs754800675
Type: single nucleotide variant
Location: chrX:21992671 (GRCh38)
Structure: AlphaFold pLDDT 95.09 · 2 PDB
Residue 340: the pabs domain; a β-strand

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

Disease context

SMS-related disorder

Similar variants

SMS p.Glu340Gly Conflicting classifications of pathogenicity ★ ⚠ same residue
SMS p.Arg116Ter Likely pathogenic ★ same condition
SMS p.Glu207Ala Uncertain significance ★ ⚠ same condition
SMS p.Glu37Asp Uncertain significance ★ ⚠ same condition
SMS p.Ile253Arg Uncertain significance ★ ⚠ same condition
SMS c.661-1C>T Likely pathogenic same condition
SMS p.Gly67Val Likely pathogenic same condition
SMS p.Thr322= 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-glu340 (accessed [today's date]).

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