Is ADSS1 p.Ser193= (c.579C>T) pathogenic?

ADSS1 p.Ser193= (c.579C>T) is classified Benign in ADSS1 (ClinVar, Multiple submitters, 5 submitters; last evaluated 2026-02-04). Common (popmax 13.5%, amr) — too common for a highly-penetrant pathogenic allele; Associated with myopathy, distal, 5.

What condition is associated with ADSS1 p.Ser193= (c.579C>T)?

ADSS1 p.Ser193= (c.579C>T) is associated with myopathy, distal, 5 (ClinVar).

ADSS1 p.Ser193=

Q: How common is ADSS1 p.Ser193= (c.579C>T) in the general population?

ADSS1 p.Ser193= (c.579C>T) is common (popmax 13.5%, amr) — too common for a highly-penetrant pathogenic allele (gnomAD).

Q: How is Adenylosuccinate synthetase-like 1-related distal myopathy inherited?

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

c.579C>T · rs12894569 · VCV1189015

Benign Multiple submitters

Classification

Benign

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 5 submitters

gnomAD v4.1

Common

common (popmax 13.5%, amr) — too common for a highly-penetrant pathogenic allele

Conditions

myopathy, distal, 5

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 -1.8	GERP -3.4
Overall
CADD	4.214	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 13.5% Admixed American · 8,119/60,014 alleles

Filtering AF 13.3% ClinGen BA1/BS1 input FAF95, joint · FAF99 13.2%

Overall 11.3% 182,795/1,613,772 alleles · common

Ancestry group	Frequency	1 in
Admixed Americangrpmax	13.5%	7
European (non-Finnish)	12%	8
Finnishnot grpmax-eligible	12%	8
Ashkenazi Jewishnot grpmax-eligible	11.3%	9
Remaining individualsnot grpmax-eligible	10.9%	9
Middle Eastern	8.83%	11
African / African-American	8.77%	11
South Asian	8.7%	11
Amishnot grpmax-eligible	3.4%	29
East Asian	1.45%	69

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: ADSS1
Protein: p.Ser193=
Coding: c.579C>T
MANE Select: NM_152328
dbSNP: rs12894569
Type: single nucleotide variant
Location: chr14:104740703 (GRCh38)
Gene constraint: LOEUF 1.245 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 93.10

Full ADSS1 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Disease context

myopathy, distal, 5 — disease report on Sugi Atlas → Associated genes, phenotypes, clinical trials & treatments

For Adenylosuccinate synthetase-like 1-related distal myopathy (Orphanet):

Inheritance: Autosomal recessive
Onset: Adolescent, Childhood

Similar variants

ADSS1 p.Ser193Phe Uncertain significance ★★ ⚠ same residue
ADSS1 c.949-2A>G Likely pathogenic ★★ same condition
ADSS1 p.Asp261Asn Pathogenic/Likely pathogenic ★★ same condition
ADSS1 p.Gln323Ter Pathogenic/Likely pathogenic ★★ same condition
ADSS1 c.193-4988T>A Uncertain significance ★★ same condition
ADSS1 c.193-5037G>T Uncertain significance ★★ same condition
ADSS1 p.Arg304His Uncertain significance ★★ ⚠ same condition
ADSS1 p.Arg431Cys 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/adss1-p-ser193 (accessed [today's date]).

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