Is ARSF p.Lys563= (c.1689G>A) pathogenic?

ARSF p.Lys563= (c.1689G>A) is classified Likely benign in ARSF (ClinVar, Single submitter, 2 submitters; last evaluated 2022-04-01). Ultra-rare (popmax 0.0263%, nfe).

How common is ARSF p.Lys563= (c.1689G>A) in the general population?

ARSF p.Lys563= (c.1689G>A) is ultra-rare (popmax 0.0263%, nfe) (gnomAD).

ARSF p.Lys563=

c.1689G>A · rs45556844 · VCV2659874

Likely benign Single submitter

Classification

Likely benign

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 2 submitters

gnomAD v4.1

Rare

ultra-rare (popmax 0.0263%, nfe)

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 1.2	GERP -0.4, phastCons 0.029
Overall
CADD	0.39	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.0263% European (non-Finnish) · 235/895,228 alleles

Filtering AF 0.0235% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.0224%

Overall 0.0225% 272/1,209,680 alleles · ultra-rare exomes 252/1,098,209 · genomes 20/111,471 · joint denominator

Ancestry group	Frequency	1 in
Finnishnot grpmax-eligible	0.043%	2,327
Remaining individualsnot grpmax-eligible	0.0273%	3,662
European (non-Finnish)grpmax	0.0263%	3,809
Middle Eastern	0.023%	4,354
Admixed American	0.00658%	15,209

Finnish shows a higher raw frequency than the grpmax group above it. gnomAD excludes bottlenecked groups — Finnish, Ashkenazi Jewish, Amish and “Remaining individuals” — from grpmax, because founder effects make their frequencies unrepresentative for filtering. The table is sorted by frequency, so an excluded group can sit above the grpmax row.

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.Lys563=
Coding: c.1689G>A
MANE Select: NM_001201539
dbSNP: rs45556844
Type: single nucleotide variant
Location: chrX:3112472 (GRCh38)
Structure: AlphaFold pLDDT 90.98

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

Similar variants

ARSF c.1102+5G>A Likely benign ★★ same type
ARSF p.Pro6= Benign ★★ same type
ARSF p.Ala112Ser Uncertain significance ★ ⚠ same type
ARSF p.Ala411Pro Uncertain significance ★ ⚠ same type
ARSF p.Ala411Thr Uncertain significance ★ ⚠ same type
ARSF p.Ala84Pro Uncertain significance ★ ⚠ same type
ARSF p.Arg103Cys Uncertain significance ★ ⚠ same type
ARSF p.Arg179His Uncertain significance ★ ⚠ same type

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-lys563 (accessed [today's date]).

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