Is RECQL p.Cys321= (c.963T>C) pathogenic?

RECQL p.Cys321= (c.963T>C) is classified Likely benign in RECQL (ClinVar, Single submitter, 1 submitter; last evaluated 2020-02-20). Absent from gnomAD v4.1.

How common is RECQL p.Cys321= (c.963T>C) in the general population?

RECQL p.Cys321= (c.963T>C) is absent from gnomAD v4.1 (gnomAD).

RECQL p.Cys321=

c.963T>C · rs2137340855 · VCV1136217

Likely benign Single submitter

Classification

Likely benign

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

gnomAD v4.1

Absent

absent from gnomAD v4.1

Computational evidence

Protein change
Missense predictors do not apply to this variant type; conservation carries the signal.
Splicing
SpliceAI	<0.2	all four deltas below 0.2 · A>C here scores Δ0.23 · evaluated, not missing
Constraint at this position
Conservation	phyloP 1.6	GERP -3.7, phastCons 1
Overall
CADD	8.121	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Absent from gnomAD v4.1. Not observed in any sequenced alleles — a rarity signal (ACMG PM2-supporting), not evidence of pathogenicity on its own.

Variant & gene context

Gene: RECQL
Protein: p.Cys321=
Coding: c.963T>C
MANE Select: NM_002907
dbSNP: rs2137340855
Type: single nucleotide variant
Location: chr12:21475811 (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 321: the helicase c-terminal domain

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

Similar variants

RECQL p.Cys321Arg Uncertain significance ★ ⚠ same residue
RECQL p.Cys321Phe Uncertain significance ★ ⚠ same residue
RECQL p.Cys321Tyr Conflicting classifications of pathogenicity ★ ⚠ same residue
RECQL p.Cys321fs 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

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-cys321 (accessed [today's date]).

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