Is RECQL p.Asp517fs (c.1549_1552del) pathogenic?

RECQL p.Asp517fs (c.15491552del) is classified Uncertain significance in RECQL (ClinVar, Single submitter, 1 submitter; last evaluated 2023-03-27). Very rare (popmax 0.00167%, amr).

How common is RECQL p.Asp517fs (c.1549_1552del) in the general population?

RECQL p.Asp517fs (c.1549_1552del) is very rare (popmax 0.00167%, amr) (gnomAD).

RECQL p.Asp517fs

c.1549_1552del · rs775188713 · VCV1774982

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

Consequence

frameshift

predicted LoF

gnomAD v4.1

Rare

very rare (popmax 0.00167%, amr)

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 12	GERP 2, phastCons 1
Overall
CADD	34.0	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 0.00167% Admixed American · 1/59,770 alleles

Overall 0.000124% 2/1,612,188 alleles · very rare exomes 1/1,460,126 · genomes 1/152,062 · joint denominator

Ancestry group	Frequency	1 in
Admixed Americangrpmax	0.00167%	59,770
European (non-Finnish)	8.48e-05%	1,179,156

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.Asp517fs
Coding: c.1549_1552del
MANE Select: NM_002907
dbSNP: rs775188713
Type: Microsatellite
Location: chr12:21471543 (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 517: the 'winged-helix domain' region; an α-helix

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

Similar variants

RECQL p.Asp517Asn Uncertain significance ★ ⚠ same residue
RECQL p.Asp517Gly Uncertain significance ★ ⚠ same residue
RECQL p.Asp517Ter Conflicting classifications of pathogenicity ★ same residue
RECQL p.Asp517= Likely benign ★ same residue
RECQL p.275FT[1] Uncertain significance ★★ same type
RECQL p.Arg528fs Uncertain significance ★★ same type
RECQL p.Asp326_Ser327insTer Uncertain significance ★★ same type
RECQL p.His548fs 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/recql-p-asp517fs (accessed [today's date]).

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