Is ARSF p.Ala122fs (c.363del) pathogenic?

ARSF p.Ala122fs (c.363del) is classified Likely benign in ARSF (ClinVar, Single submitter, 1 submitter; last evaluated 2023-01-01). Ultra-rare (popmax 0.0459%, nfe).

How common is ARSF p.Ala122fs (c.363del) in the general population?

ARSF p.Ala122fs (c.363del) is ultra-rare (popmax 0.0459%, nfe) (gnomAD).

ARSF p.Ala122fs

c.363del · rs772377819 · VCV2659868

Likely benign Single submitter

Classification

Likely benign

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

Consequence

frameshift

predicted LoF

gnomAD v4.1

Rare

ultra-rare (popmax 0.0459%, nfe)

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 5 of 11
Splicing
SpliceAI	—	not assessed · substitutions only
Constraint at this position
Conservation	phyloP 3.5	GERP 0.093, phastCons 1
Overall
CADD	22.5	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 0.0459% European (non-Finnish) · 411/895,183 alleles

Filtering AF 0.0422% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.0408%

Overall 0.0351% 425/1,210,092 alleles · ultra-rare

Ancestry group	Frequency	1 in
European (non-Finnish)grpmax	0.0459%	2,178
Remaining individualsnot grpmax-eligible	0.021%	4,759
Finnishnot grpmax-eligible	0.00429%	23,323
African / African-American	0.00349%	28,635

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: ARSF
Protein: p.Ala122fs
Coding: c.363del
MANE Select: NM_001201539
dbSNP: rs772377819
Type: Deletion
Location: chrX:3080969 (GRCh38)
Structure: AlphaFold pLDDT 90.98

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

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/arsf-p-ala122fs (accessed [today's date]).

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