Is RECQL p.Ala565Val (c.1694C>T) pathogenic?

RECQL p.Ala565Val (c.1694C>T) is classified Uncertain significance in RECQL (ClinVar, Multiple submitters, 4 submitters; last evaluated 2025-11-16). AlphaMissense: ambiguous (0.4198); Very rare (popmax 6.92e-05%).

How common is RECQL p.Ala565Val (c.1694C>T) in the general population?

RECQL p.Ala565Val (c.1694C>T) is very rare (popmax 6.92e-05%) (gnomAD).

What do computational predictors say about RECQL p.Ala565Val (c.1694C>T)?

AlphaMissense predicts ambiguous (score 0.4198) — an in-silico prediction, not a clinical call.

RECQL p.Ala565Val

c.1694C>T · rs1248986058 · VCV1046150

Uncertain significance Multiple submitters

Classification

Uncertain significance

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 4 submitters

AlphaMissense

ambiguous

0.4198 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 6.92e-05%)

Missense predictors

1/2 damaging

REVEL, SaProt · AlphaMissense no call

Computational evidence

Protein change
AlphaMissense	0.4198	ambiguous
REVEL	0.184	benign-leaning
SaProt	LLR -10.76	damaging
⇒ SaProt calls this damaging; REVEL does not; AlphaMissense makes no call.
Splicing
SpliceAI	—	not looked up on this page · why
Constraint at this position
Conservation	phyloP 12	GERP 1.7, phastCons 1
Regional constraint	o/e 0.94	unconstrained · MANE · 29 kb · p 0.095 · regional, not allelic
Overall
CADD	29.5	PHRED · no single calibrated threshold — expert panels disagree

AlphaMissense carries the ACMG weight for missense; REVEL and SaProt are independent agreement signals.

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 6.92e-05%

Overall 6.92e-05% 1/1,444,860 alleles · very rare

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.Ala565Val
Coding: c.1694C>T
MANE Select: NM_024854 · reported on NM_002907
dbSNP: rs1248986058
Type: single nucleotide variant
Location: chr12:21471072 (GRCh38)

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

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-ala565val (accessed [today's date]).

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