Is RECQL p.Phe623Leu (c.1869C>G) pathogenic?

RECQL p.Phe623Leu (c.1869C>G) is classified Uncertain significance in RECQL (ClinVar, Multiple submitters, 2 submitters; last evaluated 2024-02-20). AlphaMissense: likely benign (0.2766); Very rare (popmax 0.00136%, afr).

How common is RECQL p.Phe623Leu (c.1869C>G) in the general population?

RECQL p.Phe623Leu (c.1869C>G) is very rare (popmax 0.00136%, afr) (gnomAD).

What do computational predictors say about RECQL p.Phe623Leu (c.1869C>G)?

AlphaMissense predicts likely benign (score 0.2766) — an in-silico prediction, not a clinical call.

RECQL p.Phe623Leu

c.1869C>G · rs776400641 · VCV1352958

Uncertain significance Multiple submitters

Classification

Uncertain significance

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 2 submitters

AlphaMissense

likely benign

0.2766 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 0.00136%, afr)

Missense predictors

0/3 damaging

AlphaMissense, REVEL, SaProt

Computational evidence

Protein change
AlphaMissense	0.2766	likely benign
REVEL	0.106	moderately benign-leaning
SaProt	LLR -4.83	tolerated
⇒ AlphaMissense, REVEL and SaProt all call this tolerated.
Splicing
SpliceAI	—	not looked up on this page · why
Constraint at this position
Conservation	phyloP 0.86	GERP 0.63, phastCons 1
Regional constraint	o/e 0.51	unconstrained · MANE · 772 bp · p 0.00019 · regional, not allelic
Overall
CADD	15.94	PHRED · no single calibrated threshold — expert panels disagree

ClinVar classifies this uncertain; the computational predictors unanimously lean tolerated — 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 0.00136% African / African-American · 1/73,364 alleles

Filtering AF 2.8e-05% ClinGen BA1/BS1 input FAF95, joint · FAF99 1.1e-05%

Overall 0.000187% 3/1,605,320 alleles · very rare

Ancestry group	Frequency	1 in
African / African-Americangrpmax	0.00136%	73,364
European (non-Finnish)	0.00017%	588,585

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.Phe623Leu
Coding: c.1869C>G
MANE Select: NM_024854 · reported on NM_002907
dbSNP: rs776400641
Type: single nucleotide variant
Location: chr12:21470275 (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-phe623leu (accessed [today's date]).

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