Is RECQL4 p.Pro503Ser (c.1507C>T) pathogenic?

RECQL4 p.Pro503Ser (c.1507C>T) is classified Uncertain significance in RECQL4 (ClinVar, Single submitter, 1 submitter; last evaluated 2024-10-02). AlphaMissense: likely benign (0.1697); Absent from gnomAD v4.1; Associated with Inborn genetic diseases.

What condition is associated with RECQL4 p.Pro503Ser (c.1507C>T)?

RECQL4 p.Pro503Ser (c.1507C>T) is associated with Inborn genetic diseases (ClinVar).

How common is RECQL4 p.Pro503Ser (c.1507C>T) in the general population?

RECQL4 p.Pro503Ser (c.1507C>T) is absent from gnomAD v4.1 (gnomAD).

What do computational predictors say about RECQL4 p.Pro503Ser (c.1507C>T)?

AlphaMissense predicts likely benign (score 0.1697) — an in-silico prediction, not a clinical call.

RECQL4 p.Pro503Ser

c.1507C>T · VCV3431841

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.1697 · ACMG-weighted

gnomAD v4.1

Absent

absent from gnomAD v4.1

Missense predictors

1/2 damaging

AlphaMissense, SaProt

Conditions

Inborn genetic diseases

Computational evidence

Protein change
AlphaMissense	0.1697	likely benign
SaProt	LLR -11.04	damaging
⇒ SaProt calls this damaging; AlphaMissense does not.
Splicing
SpliceAI	<0.2	all four deltas below 0.2 · G>C here scores Δ0.37 · evaluated, not missing
Constraint at this position
Conservation	phyloP 7.7	GERP 0.83, phastCons 1
Regional constraint	o/e 1.39	unconstrained · MANE · 6,350 bp · p 1.8e-56 · regional, not allelic
Overall
CADD	18.06	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

Absent from gnomAD v4.1. Not observed in any sequenced alleles — a rarity signal (ACMG PM2-supporting), not evidence of pathogenicity on its own.

Variant & gene context

Gene: RECQL4
Protein: p.Pro503Ser
Coding: c.1507C>T
MANE Select: NM_004260
Type: single nucleotide variant
Location: chr8:144515049 (GRCh38)
Gene constraint: LOEUF 1.519 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 68.32 · 2 PDB
Residue 503: the helicase atp-binding domain; a binding site; a β-strand

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

Similar variants

RECQL4 p.Pro503Ala Uncertain significance ★ ⚠ same residue
RECQL4 p.Ala1001Thr Uncertain significance ★★ ⚠ same condition
RECQL4 p.Ala1066Thr Uncertain significance ★★ ⚠ same condition
RECQL4 p.Ala1174Pro Uncertain significance ★★ ⚠ same condition
RECQL4 p.Ala122Ser Uncertain significance ★★ ⚠ same condition
RECQL4 p.Ala152Gly Uncertain significance ★★ ⚠ same condition
RECQL4 p.Ala152Thr Uncertain significance ★★ ⚠ same condition
RECQL4 p.Ala152Val Uncertain significance ★★ ⚠ 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-pro503ser (accessed [today's date]).

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