Is SMS p.Arg130Cys (c.388C>T) pathogenic?

SMS p.Arg130Cys (c.388C>T) is classified Pathogenic in SMS (ClinVar, Single submitter, 2 submitters; last evaluated 2021-01-07). AlphaMissense: likely pathogenic (0.6546); Absent from gnomAD v4.1; Associated with syndromic X-linked intellectual disability Snyder type.

What condition is associated with SMS p.Arg130Cys (c.388C>T)?

SMS p.Arg130Cys (c.388C>T) is associated with syndromic X-linked intellectual disability Snyder type (ClinVar).

How common is SMS p.Arg130Cys (c.388C>T) in the general population?

SMS p.Arg130Cys (c.388C>T) is absent from gnomAD v4.1 (gnomAD).

How is X-linked intellectual disability, Snyder type inherited?

Typically X-linked recessive (Orphanet). A genetic counselor can assess individual risk for a family.

What do computational predictors say about SMS p.Arg130Cys (c.388C>T)?

AlphaMissense predicts likely pathogenic (score 0.6546) — an in-silico prediction, not a clinical call.

SMS p.Arg130Cys

c.388C>T · rs1602210346 · VCV816629

Pathogenic Single submitter

Classification

Pathogenic

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 2 submitters

AlphaMissense

likely pathogenic

0.6546 · ACMG-weighted

gnomAD v4.1

Absent

absent from gnomAD v4.1

Missense predictors

3/3 damaging

AlphaMissense, REVEL, SaProt

Conditions

syndromic X-linked intellectual disability Snyder type

Computational evidence

Protein change
AlphaMissense	0.6546	likely pathogenic ✓ concordant with ClinVar
REVEL	0.712	pathogenic-leaning
SaProt	LLR -12.10	damaging
⇒ AlphaMissense, REVEL and SaProt all call this damaging.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 4.8	GERP 1.3, phastCons 1
Regional constraint	o/e 0.34	constrained · MANE · 22 kb · p 3.7e-21 · regional, not allelic
Overall
CADD	24.1	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

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.Arg130Cys
Coding: c.388C>T
MANE Select: NM_004595
dbSNP: rs1602210346
Type: single nucleotide variant
Location: chrX:21977119 (GRCh38)
Structure: AlphaFold pLDDT 95.09 · 2 PDB
Residue 130: the pabs domain

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

Disease context

syndromic X-linked intellectual disability Snyder type — disease report on Sugi Atlas → Associated genes, phenotypes, clinical trials & treatments

For X-linked intellectual disability, Snyder type (Orphanet):

Inheritance: X-linked recessive
Onset: Adolescent, Childhood, Infancy

Similar variants

SMS p.Arg130His Uncertain significance ★ ⚠ same residue
SMS p.Arg234Ter Pathogenic/Likely pathogenic ★★ same condition
SMS p.Gly203Asp Pathogenic ★★ same condition
SMS p.Gly56Ser Pathogenic ★★ ⚠ same condition
SMS p.Ile196Thr Likely pathogenic ★★ same condition
SMS p.Pro112Leu Pathogenic/Likely pathogenic ★★ ⚠ same condition
SMS c.1061+2T>C Uncertain significance ★★ same condition
SMS p.Gly333Arg Uncertain significance ★★ ⚠ 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-arg130cys (accessed [today's date]).

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