Is RECQL p.Cys321Phe (c.962G>T) pathogenic?

RECQL p.Cys321Phe (c.962G>T) is classified Uncertain significance in RECQL (ClinVar, Single submitter, 1 submitter; last evaluated 2026-06-13). AlphaMissense: likely pathogenic (0.9448); Absent from gnomAD v4.1.

How common is RECQL p.Cys321Phe (c.962G>T) in the general population?

RECQL p.Cys321Phe (c.962G>T) is absent from gnomAD v4.1 (gnomAD).

What do computational predictors say about RECQL p.Cys321Phe (c.962G>T)?

AlphaMissense predicts likely pathogenic (score 0.9448) — an in-silico prediction, not a clinical call.

RECQL p.Cys321Phe

c.962G>T · VCV4863137

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely pathogenic

0.9448 · ACMG-weighted

gnomAD v4.1

Absent

absent from gnomAD v4.1

Missense predictors

3/3 damaging

AlphaMissense, REVEL, SaProt

Computational evidence

Protein change
AlphaMissense	0.9448	likely pathogenic
REVEL	0.713	pathogenic-leaning
SaProt	LLR -15.68	damaging
⇒ AlphaMissense, REVEL and SaProt all call this damaging.
Splicing
SpliceAI	Δ0.26	acceptor gain · deltas
Pangolin	Δ0.33	gain · loss 0.26 · agrees with SpliceAI · independent
Constraint at this position
Conservation	phyloP 7.6	GERP 1.9, phastCons 1
Regional constraint	o/e 0.94	unconstrained · MANE · 29 kb · p 0.095 · regional, not allelic
Overall
CADD	33.0	PHRED · no single calibrated threshold — expert panels disagree

ClinVar classifies this uncertain; the computational predictors unanimously lean damaging — a triage signal, not a reclassification

AlphaMissense carries the ACMG weight for missense; REVEL and SaProt are independent agreement signals.

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.Cys321Phe
Coding: c.962G>T
MANE Select: NM_002907
Type: single nucleotide variant
Location: chr12:21475812 (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.Cys321Tyr Conflicting classifications of pathogenicity ★ ⚠ same residue
RECQL p.Cys321= Likely benign ★ 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-cys321phe (accessed [today's date]).

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