Is RECQL4 p.Pro437Ser (c.1309C>T) pathogenic?

RECQL4 p.Pro437Ser (c.1309C>T) is classified Likely benign in RECQL4 (ClinVar, Single submitter, 1 submitter; last evaluated 2025-11-24). AlphaMissense: likely benign (0.0666); Very rare (popmax 0.00329%, sas); Associated with Baller-Gerold syndrome.

What condition is associated with RECQL4 p.Pro437Ser (c.1309C>T)?

RECQL4 p.Pro437Ser (c.1309C>T) is associated with Baller-Gerold syndrome (ClinVar).

How common is RECQL4 p.Pro437Ser (c.1309C>T) in the general population?

RECQL4 p.Pro437Ser (c.1309C>T) is very rare (popmax 0.00329%, sas) (gnomAD).

What do computational predictors say about RECQL4 p.Pro437Ser (c.1309C>T)?

AlphaMissense predicts likely benign (score 0.0666) — an in-silico prediction, not a clinical call.

RECQL4 p.Pro437Ser

c.1309C>T · rs760413890 · VCV704425

Likely benign Single submitter

Classification

Likely benign

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.0666 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 0.00329%, sas)

Missense predictors

0/2 damaging

AlphaMissense, SaProt

Conditions

Baller-Gerold syndrome

Computational evidence

Protein change
AlphaMissense	0.0666	likely benign
SaProt	LLR -6.86	tolerated
⇒ AlphaMissense and SaProt both call this tolerated.
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 0.033	GERP -1.9
Regional constraint	o/e 1.39	unconstrained · MANE · 6,350 bp · p 1.8e-56 · regional, not allelic
Overall
CADD	0.511	PHRED · no single calibrated threshold — expert panels disagree

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

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.00329% South Asian · 3/91,088 alleles

Filtering AF 0.000875% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.000605%

Overall 0.0118% 190/1,612,702 alleles · very rare exomes 146/1,460,462 · genomes 44/152,240 · joint denominator

Ancestry group	Frequency	1 in
Finnishnot grpmax-eligible	0.27%	370
South Asiangrpmax	0.00329%	30,363
Remaining individualsnot grpmax-eligible	0.0032%	31,225
European (non-Finnish)	0.00127%	78,657

Finnish shows a higher raw frequency than the grpmax group above it. gnomAD excludes bottlenecked groups — Finnish, Ashkenazi Jewish, Amish and “Remaining individuals” — from grpmax, because founder effects make their frequencies unrepresentative for filtering. The table is sorted by frequency, so an excluded group can sit above the grpmax row.

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.Pro437Ser
Coding: c.1309C>T
MANE Select: NM_004260
dbSNP: rs760413890
Type: single nucleotide variant
Location: chr8:144515407 (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.Pro437= Likely benign ★ same residue
RECQL4 p.Pro437Thr 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
RECQL4 c.1705-1G>A 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-pro437ser (accessed [today's date]).

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