Is RECQL4 p.Phe409= (c.1227C>T) pathogenic?

RECQL4 p.Phe409= (c.1227C>T) is classified Likely benign in RECQL4 (ClinVar, Multiple submitters, 2 submitters; last evaluated 2026-03-01). Very rare (popmax 0.00322%, nfe); Associated with Baller-Gerold syndrome.

What condition is associated with RECQL4 p.Phe409= (c.1227C>T)?

RECQL4 p.Phe409= (c.1227C>T) is associated with Baller-Gerold syndrome (ClinVar).

How common is RECQL4 p.Phe409= (c.1227C>T) in the general population?

RECQL4 p.Phe409= (c.1227C>T) is very rare (popmax 0.00322%, nfe) (gnomAD).

RECQL4 p.Phe409=

c.1227C>T · rs1060504219 · VCV414232

Likely benign Multiple submitters

Classification

Likely benign

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 2 submitters

gnomAD v4.1

Rare

very rare (popmax 0.00322%, nfe)

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>T here scores Δ0.32 · evaluated, not missing
Constraint at this position
Conservation	phyloP -1.6	GERP -3.6
Overall
CADD	0.97	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.00322% European (non-Finnish) · 38/1,179,720 alleles

Filtering AF 0.00239% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.0021%

Overall 0.00242% 39/1,612,434 alleles · very rare exomes 38/1,460,258 · genomes 1/152,176 · joint denominator

Ancestry group	Frequency	1 in
European (non-Finnish)grpmax	0.00322%	31,045
East Asian	0.00223%	44,878

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.Phe409=
Coding: c.1227C>T
MANE Select: NM_004260
dbSNP: rs1060504219
Type: single nucleotide variant
Location: chr8:144515795 (GRCh38)
Gene constraint: LOEUF 1.519 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 68.32 · 2 PDB

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.Phe409Leu Conflicting classifications of pathogenicity ★ 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
RECQL4 c.1705-1G>A Likely pathogenic ★★ same condition
RECQL4 c.1705-1G>C 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-phe409 (accessed [today's date]).

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