Is RECQL p.Arg455Pro (c.1364G>C) pathogenic?

RECQL p.Arg455Pro (c.1364G>C) is classified Uncertain significance in RECQL (ClinVar, Multiple submitters, 3 submitters; last evaluated 2025-02-27). AlphaMissense: likely pathogenic (0.9968); Ultra-rare (popmax 0.0331%, mid).

How common is RECQL p.Arg455Pro (c.1364G>C) in the general population?

RECQL p.Arg455Pro (c.1364G>C) is ultra-rare (popmax 0.0331%, mid) (gnomAD).

What do computational predictors say about RECQL p.Arg455Pro (c.1364G>C)?

AlphaMissense predicts likely pathogenic (score 0.9968) — an in-silico prediction, not a clinical call.

RECQL p.Arg455Pro

c.1364G>C · rs778148225 · VCV854342

Uncertain significance Multiple submitters

Classification

Uncertain significance

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 3 submitters

AlphaMissense

likely pathogenic

0.9968 · ACMG-weighted

gnomAD v4.1

Rare

ultra-rare (popmax 0.0331%, mid)

Missense predictors

3/3 damaging

AlphaMissense, REVEL, SaProt

Computational evidence

Protein change
AlphaMissense	0.9968	likely pathogenic · top 2% in RECQL
REVEL	0.788	moderately pathogenic-leaning
SaProt	LLR -12.52	damaging
⇒ AlphaMissense, REVEL and SaProt all call this damaging.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 3.3	GERP 2, phastCons 1
Regional constraint	o/e 0.94	unconstrained · MANE · 29 kb · p 0.095 · regional, not allelic
Overall
CADD	32.0	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; REVEL and SaProt are independent agreement signals.

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.0331% Middle Eastern · 2/6,050 alleles

Filtering AF 0.00583% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.00242%

Overall 0.000683% 11/1,611,568 alleles · ultra-rare exomes 11/1,459,486 · genomes 0/152,082 · joint denominator

Ancestry group	Frequency	1 in
Middle Easterngrpmax	0.0331%	3,025
Remaining individualsnot grpmax-eligible	0.00481%	20,801
African / African-American	0.00133%	74,928
European (non-Finnish)	0.000424%	235,665

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: RECQL
Protein: p.Arg455Pro
Coding: c.1364G>C
MANE Select: NM_002907
dbSNP: rs778148225
Type: single nucleotide variant
Location: chr12:21473634 (GRCh38)
Gene constraint: LOEUF 1.235 · pLI <0.01 · ClinGen HI gene assoc. with recessive phenotype (gnomAD)
Structure: AlphaFold pLDDT 86.55 · 7 PDB
Residue 455: an α-helix

Full RECQL gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Similar variants

RECQL p.Arg455Cys Uncertain significance ★★ ⚠ same residue
RECQL p.Arg455His Uncertain significance ★★ ⚠ same residue
RECQL p.Arg455Ser Uncertain significance ★★ ⚠ same residue
RECQL p.Arg455del Conflicting classifications of pathogenicity ★ same residue
RECQL c.1098+1G>A Uncertain significance ★★ same type
RECQL c.1216+3A>G Uncertain significance ★★ same type
RECQL c.1217-3C>T Uncertain significance ★★ same type
RECQL c.1355+1G>A Uncertain significance ★★ same type

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/recql-p-arg455pro (accessed [today's date]).

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