Is RECQL p.Asp517Ter (c.1548dup) pathogenic?

RECQL p.Asp517Ter (c.1548dup) is classified Conflicting classifications of pathogenicity in RECQL (ClinVar, Conflicting submitters, 2 submitters; last evaluated 2022-02-17). Ultra-rare (popmax 0.0111%, eas); Associated with hereditary breast ovarian cancer syndrome.

What condition is associated with RECQL p.Asp517Ter (c.1548dup)?

RECQL p.Asp517Ter (c.1548dup) is associated with hereditary breast ovarian cancer syndrome (ClinVar).

How common is RECQL p.Asp517Ter (c.1548dup) in the general population?

RECQL p.Asp517Ter (c.1548dup) is ultra-rare (popmax 0.0111%, eas) (gnomAD).

How is Hereditary breast and/or ovarian cancer syndrome inherited?

Typically Autosomal dominant (Orphanet). A genetic counselor can assess individual risk for a family.

RECQL p.Asp517Ter

c.1548dup · rs1942965081 · VCV830284

Conflicting classifications of pathogenicity Conflicting submitters

Classification

Conflicting classifications of pathogenicity

ClinVar

Review

Conflicting submitters ★☆☆☆

ClinVar · 2 submitters

Consequence

nonsense (stop-gain)

predicted LoF

gnomAD v4.1

Rare

ultra-rare (popmax 0.0111%, eas)

Conditions

hereditary breast ovarian cancer syndrome

Computational evidence

Protein change
Missense predictors do not apply to this variant type; conservation carries the signal.
Consequence	nonsense (stop-gain)	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 7.5	GERP 2, phastCons 1

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

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.0111% East Asian · 5/44,864 alleles

Filtering AF 0.00435% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.00276%

Overall 0.000411% 6/1,460,074 alleles · ultra-rare

Ancestry group	Frequency	1 in
East Asiangrpmax	0.0111%	8,973
European (non-Finnish)	8.48e-05%	1,179,112

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.Asp517Ter
Coding: c.1548dup
MANE Select: NM_002907
dbSNP: rs1942965081
Type: Duplication
Location: chr12:21471546 (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

Disease context

hereditary breast ovarian cancer syndrome — disease report on Sugi Atlas → Associated genes, phenotypes, clinical trials & treatments

For Hereditary breast and/or ovarian cancer syndrome (Orphanet):

Inheritance: Autosomal dominant
Onset: Adult, Elderly

Similar variants

RECQL p.Asp517Asn Uncertain significance ★ ⚠ same residue
RECQL p.Asp517fs Uncertain significance ★ same residue
RECQL p.Asp517Gly Uncertain significance ★ ⚠ same residue
RECQL p.Asp517= Likely benign ★ same residue
RECQL p.Arg454His Uncertain significance ★★ ⚠ same condition
RECQL p.Thr263Met Uncertain significance ★★ ⚠ same condition
RECQL p.Asn363Ser Benign/Likely benign ★★ same condition
RECQL p.Ala248Thr Conflicting classifications of pathogenicity ★ ⚠ 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-asp517ter (accessed [today's date]).

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