Is RECQL p.Cys138= (c.414C>T) pathogenic?

RECQL p.Cys138= (c.414C>T) is classified Likely benign in RECQL (ClinVar, Single submitter, 1 submitter; last evaluated 2019-10-25). Very rare (popmax 8.55e-05%, nfe).

How common is RECQL p.Cys138= (c.414C>T) in the general population?

RECQL p.Cys138= (c.414C>T) is very rare (popmax 8.55e-05%, nfe) (gnomAD).

RECQL p.Cys138=

c.414C>T · rs1330687345 · VCV1160552

Likely benign Single submitter

Classification

Likely benign

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

gnomAD v4.1

Rare

very rare (popmax 8.55e-05%, nfe)

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 0.88	GERP -2.5, phastCons 1
Overall
CADD	7.723	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 8.55e-05% European (non-Finnish) · 1/1,169,298 alleles

Overall 6.96e-05% 1/1,436,940 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.Cys138=
Coding: c.414C>T
MANE Select: NM_002907
dbSNP: rs1330687345
Type: single nucleotide variant
Location: chr12:21486566 (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 138: the helicase atp-binding domain

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

Similar variants

RECQL p.Cys138Phe 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-cys138 (accessed [today's date]).

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