Is RECQL4 p.Pro299= (c.897A>G) pathogenic?

RECQL4 p.Pro299= (c.897A>G) is classified Likely benign in RECQL4 (ClinVar, Multiple submitters, 2 submitters; last evaluated 2025-02-07). Very rare (popmax 0.004%, afr); Associated with Baller-Gerold syndrome.

What condition is associated with RECQL4 p.Pro299= (c.897A>G)?

RECQL4 p.Pro299= (c.897A>G) is associated with Baller-Gerold syndrome (ClinVar).

How common is RECQL4 p.Pro299= (c.897A>G) in the general population?

RECQL4 p.Pro299= (c.897A>G) is very rare (popmax 0.004%, afr) (gnomAD).

RECQL4 p.Pro299=

c.897A>G · rs1554902618 · VCV529076

Likely benign Multiple submitters

Classification

Likely benign

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 2 submitters

gnomAD v4.1

Rare

very rare (popmax 0.004%, afr)

Conditions

Baller-Gerold 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 -0.94	GERP -3.3
Overall
CADD	1.06	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.004% African / African-American · 3/74,932 alleles

Filtering AF 0.00106% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.000495%

Overall 0.00031% 5/1,613,078 alleles · very rare exomes 3/1,460,888 · genomes 2/152,190 · joint denominator

Ancestry group	Frequency	1 in
African / African-Americangrpmax	0.004%	24,977
Admixed American	0.00167%	59,996
Remaining individualsnot grpmax-eligible	0.0016%	62,446

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.Pro299=
Coding: c.897A>G
MANE Select: NM_004260
dbSNP: rs1554902618
Type: single nucleotide variant
Location: chr8:144516222 (GRCh38)
Gene constraint: LOEUF 1.519 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 68.32 · 2 PDB
Residue 299: the 'disordered' region

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

Disease context

Baller-Gerold syndrome — disease report on Sugi Atlas → Associated genes, phenotypes, clinical trials & treatments

Similar variants

RECQL4 p.Pro299Leu Uncertain significance ★★ ⚠ same residue
RECQL4 p.Pro299Ser Uncertain significance ★★ ⚠ same residue
RECQL4 p.Pro299Ala 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
RECQL4 c.1704+2T>G 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-pro299 (accessed [today's date]).

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