Is RECQL p.Lys45= (c.135A>G) pathogenic?

RECQL p.Lys45= (c.135A>G) is classified Likely benign in RECQL (ClinVar, Multiple submitters, 4 submitters; last evaluated 2023-09-11). Very rare (popmax 0.00769%, sas).

How common is RECQL p.Lys45= (c.135A>G) in the general population?

RECQL p.Lys45= (c.135A>G) is very rare (popmax 0.00769%, sas) (gnomAD).

RECQL p.Lys45=

c.135A>G · rs760544315 · VCV681432

Likely benign Multiple submitters

Classification

Likely benign

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 4 submitters

gnomAD v4.1

Rare

very rare (popmax 0.00769%, sas)

Computational evidence

Protein change
Missense predictors do not apply to this variant type; conservation carries the signal.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 0.41	GERP 1.5, phastCons 0.87
Overall
CADD	7.994	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.00769% South Asian · 7/91,068 alleles

Filtering AF 0.00367% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.00329%

Overall 0.00409% 66/1,613,798 alleles · very rare

Ancestry group	Frequency	1 in
South Asiangrpmax	0.00769%	13,010
European (non-Finnish)	0.00466%	21,452
African / African-American	0.004%	24,974
Remaining individualsnot grpmax-eligible	0.0016%	62,470

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.Lys45=
Coding: c.135A>G
MANE Select: NM_002907
dbSNP: rs760544315
Type: single nucleotide variant
Location: chr12:21491598 (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.Lys45fs Uncertain significance ★ same residue
RECQL c.1098+1G>A Uncertain significance ★★ same type
RECQL c.1216+3A>G Uncertain significance ★★ same type
RECQL c.1217-3C>T Uncertain significance ★★ same type
RECQL c.1355+1G>A Uncertain significance ★★ same type
RECQL c.1356-12A>G Uncertain significance ★★ same type
RECQL c.1667+5G>C Uncertain significance ★★ same type
RECQL c.394+1G>A 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-lys45 (accessed [today's date]).

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