Is RECQL4 p.Ser286Pro (c.856T>C) pathogenic?

RECQL4 p.Ser286Pro (c.856T>C) is classified Likely benign in RECQL4 (ClinVar, Single submitter, 1 submitter; last evaluated 2025-10-13). AlphaMissense: likely benign (0.0634); Very rare (popmax 8.48e-05%, nfe); Associated with Inborn genetic diseases.

What condition is associated with RECQL4 p.Ser286Pro (c.856T>C)?

RECQL4 p.Ser286Pro (c.856T>C) is associated with Inborn genetic diseases (ClinVar).

How common is RECQL4 p.Ser286Pro (c.856T>C) in the general population?

RECQL4 p.Ser286Pro (c.856T>C) is very rare (popmax 8.48e-05%, nfe) (gnomAD).

What do computational predictors say about RECQL4 p.Ser286Pro (c.856T>C)?

AlphaMissense predicts likely benign (score 0.0634) — an in-silico prediction, not a clinical call.

RECQL4 p.Ser286Pro

c.856T>C · VCV4628950

Likely benign Single submitter

Classification

Likely benign

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.0634 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 8.48e-05%, nfe)

Missense predictors

0/2 damaging

AlphaMissense, SaProt

Conditions

Inborn genetic diseases

Computational evidence

Protein change
AlphaMissense	0.0634	likely benign
SaProt	LLR -5.92	tolerated
⇒ AlphaMissense and SaProt both call this tolerated.
Splicing
SpliceAI	<0.2	no splice effect predicted · four deltas, not one · how we know
Constraint at this position
Conservation	phyloP 0.22	GERP -3
Regional constraint	o/e 1.39	unconstrained · MANE · 6,350 bp · p 1.8e-56 · regional, not allelic
Overall
CADD	4.58	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 8.48e-05% European (non-Finnish) · 1/1,179,522 alleles

Overall 6.2e-05% 1/1,612,150 alleles · very rare exomes 1/1,459,934 · genomes 0/152,216 · joint denominator

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.Ser286Pro
Coding: c.856T>C
MANE Select: NM_004260
Type: single nucleotide variant
Location: chr8:144516263 (GRCh38)
Gene constraint: LOEUF 1.519 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 68.32 · 2 PDB
Residue 286: the 'disordered' region

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.Ser286= Likely benign ★★ same residue
RECQL4 p.Ser286Leu Uncertain significance ★ ⚠ same residue
RECQL4 p.Ser286Trp 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

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-ser286pro (accessed [today's date]).

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