Is RECQL p.His548fs (c.1643_1644del) pathogenic?

RECQL p.His548fs (c.16431644del) is classified Uncertain significance in RECQL (ClinVar, Multiple submitters, 2 submitters; last evaluated 2024-02-07). Absent from gnomAD; Associated with RECON progeroid syndrome.

What condition is associated with RECQL p.His548fs (c.1643_1644del)?

RECQL p.His548fs (c.1643_1644del) is associated with RECON progeroid syndrome (ClinVar).

How common is RECQL p.His548fs (c.1643_1644del) in the general population?

RECQL p.His548fs (c.1643_1644del) is absent from gnomAD (gnomAD).

RECQL p.His548fs

c.1643_1644del · rs1942960300 · VCV2450947

Uncertain significance Multiple submitters

Classification

Uncertain significance

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 2 submitters

Consequence

frameshift

predicted LoF

gnomAD v4.1

Not reported

no gnomAD frequency available for this variant

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 0.04	GERP -2.5, phastCons 0.046

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

Population frequency

dbSNP / gnomAD

No gnomAD frequency available for this variant. This is missing data, not an absence: the variant may or may not be present in gnomAD. Rarity (ACMG PM2) and BA1/BS1 cannot be assessed for it.

Variant & gene context

Gene: RECQL
Protein: p.His548fs
Coding: c.1643_1644del
MANE Select: NM_002907
dbSNP: rs1942960300
Type: Microsatellite
Location: chr12:21471451 (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 548: the 'winged-helix domain' region; an α-helix

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.Arg528fs Uncertain significance ★★ same condition
RECQL p.His548Tyr Uncertain significance ★★ ⚠ same residue
RECQL p.Arg455del Conflicting classifications of pathogenicity ★ same condition
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
RECQL p.Ala459Ser Uncertain significance ★★ ⚠ same condition
RECQL p.Asp264Glu 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-his548fs (accessed [today's date]).

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