Is RECQL p.Ser482del (c.1444_1446del) pathogenic?

RECQL p.Ser482del (c.14441446del) is classified Uncertain significance in RECQL (ClinVar, Multiple submitters, 3 submitters; last evaluated 2025-10-21). Very rare (popmax 0.00334%, amr).

How common is RECQL p.Ser482del (c.1444_1446del) in the general population?

RECQL p.Ser482del (c.1444_1446del) is very rare (popmax 0.00334%, amr) (gnomAD).

RECQL p.Ser482del

c.1444_1446del · rs762926806 · VCV1414972

Uncertain significance Multiple submitters

Classification

Uncertain significance

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 3 submitters

gnomAD v4.1

Rare

very rare (popmax 0.00334%, amr)

Computational evidence

Protein change
Missense predictors do not apply to this variant type; conservation carries the signal.
Splicing
SpliceAI	—	not assessed · substitutions only
Constraint at this position
Conservation	phyloP -0.33	GERP -3.7
Overall
CADD	2.277	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.00334% Admixed American · 2/59,798 alleles

Filtering AF 0.000805% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.000651%

Overall 0.00124% 20/1,610,378 alleles · very rare exomes 17/1,458,294 · genomes 3/152,084 · joint denominator

Ancestry group	Frequency	1 in
Admixed Americangrpmax	0.00334%	29,899
African / African-American	0.00267%	37,408
European (non-Finnish)	0.00136%	73,582

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.Ser482del
Coding: c.1444_1446del
MANE Select: NM_002907
dbSNP: rs762926806
Type: Deletion
Location: chr12:21473552 (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 482: the 'winged-helix domain' region

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

Similar variants

RECQL p.Ser482Gly Uncertain significance ★★ ⚠ same residue
RECQL p.Ser482= Conflicting classifications of pathogenicity ★ same residue
RECQL p.Ser482Arg Uncertain significance ★ ⚠ same residue
RECQL p.Ser482Asn Uncertain significance ★ ⚠ same residue
RECQL p.Ser482Thr Uncertain significance ★ ⚠ same residue
RECQL c.1353_1355+1del Uncertain significance ★★ same type
RECQL c.1447+3_1447+6del Uncertain significance ★★ same type
RECQL c.1667_1667+3del 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-ser482del (accessed [today's date]).

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