Is RECQL4 p.Phe390= (c.1170T>C) pathogenic?

RECQL4 p.Phe390= (c.1170T>C) is classified Likely benign in RECQL4 (ClinVar, Multiple submitters, 6 submitters; last evaluated 2026-01-19). Ultra-rare (popmax 0.0857%, sas); Associated with Inborn genetic diseases.

What condition is associated with RECQL4 p.Phe390= (c.1170T>C)?

RECQL4 p.Phe390= (c.1170T>C) is associated with Inborn genetic diseases, Baller-Gerold syndrome, rapadilino syndrome (ClinVar).

How common is RECQL4 p.Phe390= (c.1170T>C) in the general population?

RECQL4 p.Phe390= (c.1170T>C) is ultra-rare (popmax 0.0857%, sas) (gnomAD).

RECQL4 p.Phe390=

c.1170T>C · rs768991485 · VCV459308

Likely benign Multiple submitters

Classification

Likely benign

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 6 submitters

gnomAD v4.1

Rare

ultra-rare (popmax 0.0857%, sas)

Conditions

Inborn genetic diseases

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 · A>C here scores Δ0.25 · evaluated, not missing
Constraint at this position
Conservation	phyloP 0.16	GERP -3.5
Overall
CADD	1.227	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.0857% South Asian · 78/91,028 alleles

Filtering AF 0.0703% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.0647%

Overall 0.00843% 136/1,612,894 alleles · ultra-rare exomes 125/1,460,644 · genomes 11/152,250 · joint denominator

Ancestry group	Frequency	1 in
South Asiangrpmax	0.0857%	1,167
Ashkenazi Jewishnot grpmax-eligible	0.0811%	1,233
Middle Eastern	0.033%	3,031
Remaining individualsnot grpmax-eligible	0.0144%	6,941
European (non-Finnish)	0.00186%	53,626
Admixed American	0.00167%	59,990

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.Phe390=
Coding: c.1170T>C
MANE Select: NM_004260
dbSNP: rs768991485
Type: single nucleotide variant
Location: chr8:144515852 (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

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

Also linked: Baller-Gerold syndrome rapadilino syndrome Rothmund-Thomson syndrome type 2

Similar variants

RECQL4 p.Phe390Cys Uncertain significance ★★ ⚠ same residue
RECQL4 p.Phe390Leu Uncertain significance ★ ⚠ same residue
RECQL4 p.Phe390Ser 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-phe390 (accessed [today's date]).

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