Is RECQL4 p.Pro671Arg (c.2012C>G) pathogenic?

RECQL4 p.Pro671Arg (c.2012C>G) is classified Uncertain significance in RECQL4 (ClinVar, Multiple submitters, 2 submitters; last evaluated 2026-02-01). AlphaMissense: likely benign (0.333); Absent from gnomAD v4.1; Associated with Inborn genetic diseases.

What condition is associated with RECQL4 p.Pro671Arg (c.2012C>G)?

RECQL4 p.Pro671Arg (c.2012C>G) is associated with Inborn genetic diseases, Baller-Gerold syndrome (ClinVar).

How common is RECQL4 p.Pro671Arg (c.2012C>G) in the general population?

RECQL4 p.Pro671Arg (c.2012C>G) is absent from gnomAD v4.1 (gnomAD).

What do computational predictors say about RECQL4 p.Pro671Arg (c.2012C>G)?

AlphaMissense predicts likely benign (score 0.333) — an in-silico prediction, not a clinical call.

RECQL4 p.Pro671Arg

c.2012C>G · rs889029109 · VCV848493

Uncertain significance Multiple submitters

Classification

Uncertain significance

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 2 submitters

AlphaMissense

likely benign

0.333 · ACMG-weighted

gnomAD v4.1

Absent

absent from gnomAD v4.1

Missense predictors

1/2 damaging

AlphaMissense, SaProt

Conditions

Inborn genetic diseases

Computational evidence

Protein change
AlphaMissense	0.333	likely benign
SaProt	LLR -10.45	damaging
⇒ SaProt calls this damaging; AlphaMissense does not.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 12	GERP 1.8, phastCons 1
Regional constraint	o/e 1.39	unconstrained · MANE · 6,350 bp · p 1.8e-56 · regional, not allelic
Overall
CADD	21.5	PHRED · no single calibrated threshold — expert panels disagree

AlphaMissense carries the ACMG weight for missense; SaProt is an independent agreement signal.

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: RECQL4
Protein: p.Pro671Arg
Coding: c.2012C>G
MANE Select: NM_004260
dbSNP: rs889029109
Type: single nucleotide variant
Location: chr8:144513974 (GRCh38)
Gene constraint: LOEUF 1.519 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 68.32 · 2 PDB
Residue 671: an α-helix

Full RECQL4 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Disease context

Inborn genetic diseases — disease report on Sugi Atlas → Associated genes, phenotypes, clinical trials & treatments

Also linked: Baller-Gerold syndrome

Similar variants

RECQL4 p.Pro671Leu Uncertain significance ★★ ⚠ same residue
RECQL4 p.Pro671Ser Uncertain significance ★★ same residue
RECQL4 p.Pro671Thr Uncertain significance ★★ same residue
RECQL4 p.Pro671Ala Uncertain significance ★ ⚠ same residue
RECQL4 p.Pro671= Likely benign ★ same residue
RECQL4 c.1132-1G>A Likely pathogenic ★★ same condition
RECQL4 c.1259-1G>A Pathogenic/Likely pathogenic ★★ same condition
RECQL4 c.1391-1G>A Pathogenic ★★ same condition

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/recql4-p-pro671arg (accessed [today's date]).

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