Is RECQL p.Ser182= (c.546C>T) pathogenic?

RECQL p.Ser182= (c.546C>T) is classified Likely benign in RECQL (ClinVar, Multiple submitters, 3 submitters; last evaluated 2024-04-29). Ultra-rare (popmax 0.0262%, sas).

How common is RECQL p.Ser182= (c.546C>T) in the general population?

RECQL p.Ser182= (c.546C>T) is ultra-rare (popmax 0.0262%, sas) (gnomAD).

RECQL p.Ser182=

c.546C>T · rs746587399 · VCV1747721

Likely benign Multiple submitters

Classification

Likely benign

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 3 submitters

gnomAD v4.1

Rare

ultra-rare (popmax 0.0262%, 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 0.18	GERP -2.9, phastCons 0.002
Overall
CADD	13.67	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.0262% South Asian · 22/84,088 alleles

Filtering AF 0.0177% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.0149%

Overall 0.00266% 42/1,576,786 alleles · ultra-rare

Ancestry group	Frequency	1 in
South Asiangrpmax	0.0262%	3,822
Middle Eastern	0.0168%	5,962
East Asian	0.00229%	43,756
Remaining individualsnot grpmax-eligible	0.00164%	61,066
European (non-Finnish)	0.00145%	68,791

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.Ser182=
Coding: c.546C>T
MANE Select: NM_002907
dbSNP: rs746587399
Type: single nucleotide variant
Location: chr12:21483530 (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 182: the helicase atp-binding domain

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

Similar variants

RECQL p.Ser182Tyr 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-ser182 (accessed [today's date]).

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