Is RECQL4 p.Pro781= (c.2343A>G) pathogenic?

RECQL4 p.Pro781= (c.2343A>G) is classified Likely benign in RECQL4 (ClinVar, Multiple submitters, 2 submitters; last evaluated 2025-05-09). Very rare (popmax 0.000848%, nfe); Associated with hereditary neoplastic syndrome.

What condition is associated with RECQL4 p.Pro781= (c.2343A>G)?

RECQL4 p.Pro781= (c.2343A>G) is associated with hereditary neoplastic syndrome, Baller-Gerold syndrome (ClinVar).

How common is RECQL4 p.Pro781= (c.2343A>G) in the general population?

RECQL4 p.Pro781= (c.2343A>G) is very rare (popmax 0.000848%, nfe) (gnomAD).

RECQL4 p.Pro781=

c.2343A>G · rs1060504215 · VCV414219

Likely benign Multiple submitters

Classification

Likely benign

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 2 submitters

gnomAD v4.1

Rare

very rare (popmax 0.000848%, nfe)

Conditions

hereditary neoplastic syndrome

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 -8.5	GERP -3.9
Overall
CADD	2.395	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.000848% European (non-Finnish) · 10/1,179,610 alleles

Filtering AF 0.000429% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.000313%

Overall 0.000623% 10/1,604,138 alleles · very rare exomes 9/1,451,910 · genomes 1/152,228 · joint denominator

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: RECQL4
Protein: p.Pro781=
Coding: c.2343A>G
MANE Select: NM_004260
dbSNP: rs1060504215
Type: single nucleotide variant
Location: chr8:144513338 (GRCh38)
Gene constraint: LOEUF 1.519 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 68.32 · 2 PDB
Residue 781: the helicase c-terminal domain; a UniProt-annotated variant site (in rts2)

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

Disease context

hereditary neoplastic syndrome — disease report on Sugi Atlas → Associated genes, phenotypes, clinical trials & treatments

Also linked: Baller-Gerold syndrome

Similar variants

RECQL4 p.Pro781Ala Uncertain significance ★ ⚠ same residue
RECQL4 p.Pro781Arg Uncertain significance ★ ⚠ same residue
RECQL4 p.Pro781Ser Uncertain significance ★ ⚠ same residue
RECQL4 p.Pro781Leu Uncertain significance ★ ⚠ 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
RECQL4 c.1704+1G>A Pathogenic/Likely 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-pro781 (accessed [today's date]).

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