Is SMS p.Ser342= (c.1026A>C) pathogenic?

SMS p.Ser342= (c.1026A>C) is classified Benign/Likely benign in SMS (ClinVar, Multiple submitters, 11 submitters; last evaluated 2026-01-27). Rare (popmax 0.685%, nfe); Associated with Inborn genetic diseases.

What condition is associated with SMS p.Ser342= (c.1026A>C)?

SMS p.Ser342= (c.1026A>C) is associated with Inborn genetic diseases, syndromic X-linked intellectual disability Snyder type (ClinVar).

How common is SMS p.Ser342= (c.1026A>C) in the general population?

SMS p.Ser342= (c.1026A>C) is rare (popmax 0.685%, nfe) (gnomAD).

SMS p.Ser342=

c.1026A>C · rs61732077 · VCV193675

Benign/Likely benign Multiple submitters

Classification

Benign/Likely benign

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 11 submitters

gnomAD v4.1

Rare

rare (popmax 0.685%, nfe)

Conditions

Inborn genetic diseases

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 -2.7	GERP -4.4
Overall
CADD	0.113	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.685% European (non-Finnish) · 6,040/881,448 alleles

Filtering AF 0.671% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.665%

Overall 0.548% 6,543/1,194,374 alleles · rare exomes 6,118/1,082,175 · genomes 425/112,199 · joint denominator

Ancestry group	Frequency	1 in
European (non-Finnish)grpmax	0.685%	146
Remaining individualsnot grpmax-eligible	0.425%	235
Ashkenazi Jewishnot grpmax-eligible	0.333%	300
Admixed American	0.129%	775
Finnishnot grpmax-eligible	0.122%	818
South Asian	0.11%	911
African / African-American	0.086%	1,163
Middle Eastern	0.0796%	1,256

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.Ser342=
Coding: c.1026A>C
MANE Select: NM_004595
dbSNP: rs61732077
Type: single nucleotide variant
Location: chrX:21992677 (GRCh38)
Structure: AlphaFold pLDDT 95.09 · 2 PDB
Residue 342: the pabs domain; a β-strand

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

Also linked: syndromic X-linked intellectual disability Snyder type

Similar variants

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
SMS p.Gly78Ala 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-ser342 (accessed [today's date]).

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