Is RECQL p.Arg528fs (c.1584_1585del) pathogenic?

RECQL p.Arg528fs (c.15841585del) is classified Uncertain significance in RECQL (ClinVar, Multiple submitters, 2 submitters; last evaluated 2023-12-28). Very rare (popmax 8.48e-05%, nfe); Associated with RECON progeroid syndrome.

What condition is associated with RECQL p.Arg528fs (c.1584_1585del)?

RECQL p.Arg528fs (c.1584_1585del) is associated with RECON progeroid syndrome (ClinVar).

How common is RECQL p.Arg528fs (c.1584_1585del) in the general population?

RECQL p.Arg528fs (c.1584_1585del) is very rare (popmax 8.48e-05%, nfe) (gnomAD).

RECQL p.Arg528fs

c.1584_1585del · rs2540320876 · VCV1775760

Uncertain significance Multiple submitters

Classification

Uncertain significance

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 2 submitters

Consequence

frameshift

predicted LoF

gnomAD v4.1

Rare

very rare (popmax 8.48e-05%, nfe)

Conditions

RECON progeroid syndrome

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 13 of 15
Splicing
SpliceAI	—	not assessed · substitutions only
Constraint at this position
Conservation	phyloP 4.6	GERP 0.75, phastCons 1

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

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 8.48e-05% European (non-Finnish) · 1/1,179,312 alleles

Overall 6.2e-05% 1/1,612,680 alleles · very rare exomes 1/1,460,614 · genomes 0/152,066 · joint denominator

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: RECQL
Protein: p.Arg528fs
Coding: c.1584_1585del
MANE Select: NM_002907
dbSNP: rs2540320876
Type: Microsatellite
Location: chr12:21471510 (GRCh38)
Gene constraint: LOEUF 1.235 · pLI <0.01 · ClinGen HI gene assoc. with recessive phenotype (gnomAD)
Structure: AlphaFold pLDDT 86.55 · 7 PDB
Residue 528: the 'winged-helix domain' region

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

Disease context

RECON progeroid syndrome — disease report on Sugi Atlas → Associated genes, phenotypes, clinical trials & treatments

Similar variants

RECQL p.His548fs Uncertain significance ★★ same condition
RECQL p.Arg455del Conflicting classifications of pathogenicity ★ same condition
RECQL p.Arg528Gly Uncertain significance ★ ⚠ same residue
RECQL p.Arg528Lys Uncertain significance ★ ⚠ same residue
RECQL p.Arg528= Likely benign ★ same residue
RECQL c.1667_1667+3del Uncertain significance ★★ same condition
RECQL c.394+1G>A Uncertain significance ★★ same condition
RECQL c.867+3A>T 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/recql-p-arg528fs (accessed [today's date]).

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