Is RECQL4 p.Ser494Phe (c.1481C>T) pathogenic?

RECQL4 p.Ser494Phe (c.1481C>T) is classified Uncertain significance in RECQL4 (ClinVar, Multiple submitters, 2 submitters; last evaluated 2025-11-17). AlphaMissense: likely pathogenic (0.6526); Very rare (popmax 0.00239%, eas); Associated with Baller-Gerold syndrome.

What condition is associated with RECQL4 p.Ser494Phe (c.1481C>T)?

RECQL4 p.Ser494Phe (c.1481C>T) is associated with Baller-Gerold syndrome (ClinVar).

How common is RECQL4 p.Ser494Phe (c.1481C>T) in the general population?

RECQL4 p.Ser494Phe (c.1481C>T) is very rare (popmax 0.00239%, eas) (gnomAD).

What do computational predictors say about RECQL4 p.Ser494Phe (c.1481C>T)?

AlphaMissense predicts likely pathogenic (score 0.6526) — an in-silico prediction, not a clinical call.

RECQL4 p.Ser494Phe

c.1481C>T · rs1198334062 · VCV1903921

Uncertain significance Multiple submitters

Classification

Uncertain significance

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 2 submitters

AlphaMissense

likely pathogenic

0.6526 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 0.00239%, eas)

Missense predictors

2/2 damaging

AlphaMissense, SaProt

Conditions

Baller-Gerold syndrome

Computational evidence

Protein change
AlphaMissense	0.6526	likely pathogenic
SaProt	LLR -13.77	damaging
⇒ AlphaMissense and SaProt both call this damaging.
Splicing
SpliceAI	<0.2	all four deltas below 0.2 · G>T here scores Δ0.25 · evaluated, not missing
Constraint at this position
Conservation	phyloP 6.6	GERP -0.48, phastCons 1
Regional constraint	o/e 1.39	unconstrained · MANE · 6,350 bp · p 1.8e-56 · regional, not allelic
Overall
CADD	22.1	PHRED · no single calibrated threshold — expert panels disagree

ClinVar classifies this uncertain; the computational predictors unanimously lean damaging — a triage signal, not a reclassification

AlphaMissense carries the ACMG weight for missense; SaProt is an independent agreement signal.

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.00239% East Asian · 1/41,834 alleles

Filtering AF 0.000298% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.000215%

Overall 0.000575% 9/1,565,670 alleles · very rare exomes 9/1,413,342 · genomes 0/152,328 · joint denominator

Ancestry group	Frequency	1 in
East Asiangrpmax	0.00239%	41,834
European (non-Finnish)	0.000692%	144,526

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.Ser494Phe
Coding: c.1481C>T
MANE Select: NM_004260
dbSNP: rs1198334062
Type: single nucleotide variant
Location: chr8:144515152 (GRCh38)
Gene constraint: LOEUF 1.519 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 68.32 · 2 PDB
Residue 494: the helicase atp-binding domain; a turn

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 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
RECQL4 c.2059-1G>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-ser494phe (accessed [today's date]).

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