Is RECQL4 p.Pro671Ser (c.2011C>T) pathogenic?

RECQL4 p.Pro671Ser (c.2011C>T) is classified Uncertain significance in RECQL4 (ClinVar, Multiple submitters, 2 submitters; last evaluated 2025-03-20). AlphaMissense: ambiguous (0.3862); Very rare (popmax 0.000433%, nfe); Associated with Baller-Gerold syndrome.

What condition is associated with RECQL4 p.Pro671Ser (c.2011C>T)?

RECQL4 p.Pro671Ser (c.2011C>T) is associated with Baller-Gerold syndrome (ClinVar).

How common is RECQL4 p.Pro671Ser (c.2011C>T) in the general population?

RECQL4 p.Pro671Ser (c.2011C>T) is very rare (popmax 0.000433%, nfe) (gnomAD).

What do computational predictors say about RECQL4 p.Pro671Ser (c.2011C>T)?

AlphaMissense predicts ambiguous (score 0.3862) — an in-silico prediction, not a clinical call.

RECQL4 p.Pro671Ser

c.2011C>T · rs1256215770 · VCV641485

Uncertain significance Multiple submitters

Classification

Uncertain significance

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 2 submitters

AlphaMissense

ambiguous

0.3862 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 0.000433%, nfe)

Conditions

Baller-Gerold syndrome

Computational evidence

Protein change
AlphaMissense	0.3862	ambiguous
SaProt	LLR -8.80	tolerated
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 12	GERP 1.8, phastCons 1
Regional constraint	o/e 1.39	unconstrained · MANE · 6,350 bp · p 1.8e-56 · regional, not allelic
Overall
CADD	23.6	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 0.000433% European (non-Finnish) · 5/1,155,104 alleles

Filtering AF 0.000127% ClinGen BA1/BS1 input FAF95, joint · FAF99 9.2e-05%

Overall 0.000384% 6/1,564,324 alleles · very rare exomes 6/1,412,148 · genomes 0/152,176 · joint denominator

Ancestry group	Frequency	1 in
Remaining individualsnot grpmax-eligible	0.00165%	60,614
European (non-Finnish)grpmax	0.000433%	231,021

Remaining individuals 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.Pro671Ser
Coding: c.2011C>T
MANE Select: NM_004260
dbSNP: rs1256215770
Type: single nucleotide variant
Location: chr8:144513975 (GRCh38)
Gene constraint: LOEUF 1.519 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 68.32 · 2 PDB
Residue 671: an α-helix

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.Pro671Arg Uncertain significance ★★ ⚠ same residue
RECQL4 p.Pro671Leu Uncertain significance ★★ ⚠ same residue
RECQL4 p.Pro671Thr Uncertain significance ★★ same residue
RECQL4 p.Pro671Ala Uncertain significance ★ ⚠ same residue
RECQL4 p.Pro671= Likely benign ★ 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-pro671ser (accessed [today's date]).

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