Is RECQL4 p.Pro964= (c.2892C>T) pathogenic?

RECQL4 p.Pro964= (c.2892C>T) is classified Likely benign in RECQL4 (ClinVar, Single submitter, 1 submitter; last evaluated 2024-12-29). Ultra-rare (popmax 0.0187%, sas); Associated with Baller-Gerold syndrome.

What condition is associated with RECQL4 p.Pro964= (c.2892C>T)?

RECQL4 p.Pro964= (c.2892C>T) is associated with Baller-Gerold syndrome (ClinVar).

How common is RECQL4 p.Pro964= (c.2892C>T) in the general population?

RECQL4 p.Pro964= (c.2892C>T) is ultra-rare (popmax 0.0187%, sas) (gnomAD).

RECQL4 p.Pro964=

c.2892C>T · rs776537316 · VCV1596341

Likely benign Single submitter

Classification

Likely benign

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

gnomAD v4.1

Rare

ultra-rare (popmax 0.0187%, sas)

Conditions

Baller-Gerold syndrome

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 · G>C here scores Δ0.23 · evaluated, not missing
Constraint at this position
Conservation	phyloP -0.55	GERP -3.9, phastCons 0.001
Overall
CADD	3.799	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.0187% South Asian · 17/91,090 alleles

Filtering AF 0.0118% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.00976%

Overall 0.00112% 18/1,612,552 alleles · ultra-rare exomes 16/1,460,202 · genomes 2/152,350 · joint denominator

Ancestry group	Frequency	1 in
South Asiangrpmax	0.0187%	5,358
Remaining individualsnot grpmax-eligible	0.0016%	62,466

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.Pro964=
Coding: c.2892C>T
MANE Select: NM_004260
dbSNP: rs776537316
Type: single nucleotide variant
Location: chr8:144512555 (GRCh38)
Gene constraint: LOEUF 1.519 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 68.32 · 2 PDB
Residue 964: an α-helix; a UniProt-annotated variant site (in rts2); a UniProt-annotated variant site (in)

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.Pro964Leu Uncertain significance ★★ ⚠ same residue
RECQL4 p.Pro964Arg Uncertain significance ★ ⚠ same residue
RECQL4 p.Pro964Ser Uncertain significance ★ ⚠ same residue
RECQL4 p.Pro964Thr Uncertain significance ★ ⚠ same residue
RECQL4 p.Pro964His 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

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-pro964 (accessed [today's date]).

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