Is ARSG p.Ser235fs (c.701dup) pathogenic?

ARSG p.Ser235fs (c.701dup) is classified Pathogenic/Likely pathogenic in ARSG (ClinVar, Multiple submitters, 2 submitters; last evaluated 2025-06-11). Very rare (popmax 0.00746%, nfe); Associated with ARSG-related disorder.

What condition is associated with ARSG p.Ser235fs (c.701dup)?

ARSG p.Ser235fs (c.701dup) is associated with ARSG-related disorder (ClinVar).

How common is ARSG p.Ser235fs (c.701dup) in the general population?

ARSG p.Ser235fs (c.701dup) is very rare (popmax 0.00746%, nfe) (gnomAD).

ARSG p.Ser235fs

c.701dup · rs769480000 · VCV849065

Pathogenic/Likely pathogenic Multiple submitters

Classification

Pathogenic/Likely pathogenic

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 2 submitters

Consequence

frameshift

predicted LoF

gnomAD v4.1

Rare

very rare (popmax 0.00746%, nfe)

Conditions

ARSG-related disorder

Computational evidence

Protein change
Missense predictors do not apply to this variant type; conservation carries the signal.
Consequence	frameshift	predicted loss-of-function
NMD	predicted	premature termination codon in exon 6 of 12
Splicing
SpliceAI	—	not assessed · substitutions only
Constraint at this position
Conservation	phyloP 6.4	GERP -0.52, phastCons 1
Overall
CADD	29.8	PHRED · no single calibrated threshold — expert panels disagree

Predicted loss-of-function is descriptive, not an applied PVS1 code.

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.00746% European (non-Finnish) · 88/1,180,032 alleles

Filtering AF 0.00615% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.00573%

Overall 0.00564% 91/1,614,064 alleles · very rare

Ancestry group	Frequency	1 in
European (non-Finnish)grpmax	0.00746%	13,409
Remaining individualsnot grpmax-eligible	0.0032%	31,242
African / African-American	0.00133%	74,936

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: ARSG
Protein: p.Ser235fs
Coding: c.701dup
MANE Select: NM_001267727
dbSNP: rs769480000
Type: Duplication
Location: chr17:68356800 (GRCh38)
Gene constraint: LOEUF 0.996 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 91.90

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

Disease context

ARSG-related disorder

Similar variants

ARSG p.Ser235= Likely benign ★ same residue
ARSG c.1091+1G>A Likely pathogenic ★★ same condition
ARSG c.982+2T>G Likely pathogenic ★★ same condition
ARSG p.Ser443fs Pathogenic/Likely pathogenic ★★ same condition
ARSG p.Thr31fs Pathogenic/Likely pathogenic ★★ same condition
ARSG p.Thr335Met Uncertain significance ★★ ⚠ same condition
ARSG c.1304-1G>A Likely pathogenic ★ same condition
ARSG p.Gln334Ter Likely pathogenic ★ 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/arsg-p-ser235fs (accessed [today's date]).

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