Is RECQL p.Ala57fs (c.169del) pathogenic?

RECQL p.Ala57fs (c.169del) is classified Uncertain significance in RECQL (ClinVar, Multiple submitters, 2 submitters; last evaluated 2023-06-08). Very rare (popmax 0.000339%, nfe).

How common is RECQL p.Ala57fs (c.169del) in the general population?

RECQL p.Ala57fs (c.169del) is very rare (popmax 0.000339%, nfe) (gnomAD).

RECQL p.Ala57fs

c.169del · rs1040950644 · VCV1004445

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 0.000339%, nfe)

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 3 of 15
Splicing
SpliceAI	—	not assessed · substitutions only
Constraint at this position
Conservation	phyloP 2.7	GERP -0.19, phastCons 0.16
Overall
CADD	23.4	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 0.000339% European (non-Finnish) · 4/1,178,560 alleles

Filtering AF 7.9e-05% ClinGen BA1/BS1 input FAF95, joint · FAF99 5.4e-05%

Overall 0.000249% 4/1,608,014 alleles · very rare

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.Ala57fs
Coding: c.169del
MANE Select: NM_002907
dbSNP: rs1040950644
Type: Deletion
Location: chr12:21491564 (GRCh38)
Gene constraint: LOEUF 1.235 · pLI <0.01 · ClinGen HI gene assoc. with recessive phenotype (gnomAD)
Structure: AlphaFold pLDDT 86.55 · 7 PDB

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

Similar variants

RECQL p.Ala57Pro Uncertain significance ★★ ⚠ same residue
RECQL p.Ala57Thr Uncertain significance ★ ⚠ same residue
RECQL p.Ala57= Likely benign ★ 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
RECQL p.Arg212del Uncertain significance ★★ same type
RECQL p.Asn488fs 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-ala57fs (accessed [today's date]).

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