Is SMS p.Asp201= (c.603C>T) pathogenic?

SMS p.Asp201= (c.603C>T) is classified Likely benign in SMS (ClinVar, Single submitter, 1 submitter; last evaluated 2017-07-19). Ultra-rare (popmax 0.0372%, amr); Associated with Inborn genetic diseases.

What condition is associated with SMS p.Asp201= (c.603C>T)?

SMS p.Asp201= (c.603C>T) is associated with Inborn genetic diseases (ClinVar).

How common is SMS p.Asp201= (c.603C>T) in the general population?

SMS p.Asp201= (c.603C>T) is ultra-rare (popmax 0.0372%, amr) (gnomAD).

SMS p.Asp201=

c.603C>T · rs141565064 · VCV1751229

Likely benign Single submitter

Classification

Likely benign

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

gnomAD v4.1

Rare

ultra-rare (popmax 0.0372%, amr)

Conditions

Inborn genetic diseases

Computational evidence

Protein change
Missense predictors do not apply to this variant type; conservation carries the signal.
REVEL	0.128	moderately benign-leaning
Splicing
SpliceAI	<0.2	all four deltas below 0.2 · C>G here scores Δ0.22 · evaluated, not missing
Constraint at this position
Conservation	phyloP -0.49	GERP -4.4, phastCons 0.12
Overall
CADD	4.537	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.0372% Admixed American · 17/45,678 alleles

Filtering AF 0.0237% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.0194%

Overall 0.00274% 33/1,206,385 alleles · ultra-rare

Ancestry group	Frequency	1 in
Admixed Americangrpmax	0.0372%	2,687
African / African-American	0.0158%	6,331
Remaining individualsnot grpmax-eligible	0.00842%	11,880
South Asian	0.00176%	56,759
European (non-Finnish)	0.000224%	446,090

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.Asp201=
Coding: c.603C>T
MANE Select: NM_004595
dbSNP: rs141565064
Type: single nucleotide variant
Location: chrX:21978057 (GRCh38)
Structure: AlphaFold pLDDT 95.09 · 2 PDB
Residue 201: the pabs domain; a binding site

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-asp201 (accessed [today's date]).

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