Is RECQL p.Ala641Val (c.1922C>T) pathogenic?

RECQL p.Ala641Val (c.1922C>T) is classified Uncertain significance in RECQL (ClinVar, Multiple submitters, 2 submitters; last evaluated 2024-02-29). AlphaMissense: likely benign (0.091); Very rare (popmax 0.00017%, nfe).

How common is RECQL p.Ala641Val (c.1922C>T) in the general population?

RECQL p.Ala641Val (c.1922C>T) is very rare (popmax 0.00017%, nfe) (gnomAD).

What do computational predictors say about RECQL p.Ala641Val (c.1922C>T)?

AlphaMissense predicts likely benign (score 0.091) — an in-silico prediction, not a clinical call.

RECQL p.Ala641Val

c.1922C>T · rs1942902579 · VCV967492

Uncertain significance Multiple submitters

Classification

Uncertain significance

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 2 submitters

AlphaMissense

likely benign

0.091 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 0.00017%, nfe)

Missense predictors

0/3 damaging

AlphaMissense, REVEL, SaProt

⚠ Built without this gene's context — gene constraint and dosage, protein structure, pathways, panels and related-variant links were not looked up for this page. why

Computational evidence

Protein change
AlphaMissense	0.091	likely benign
REVEL	0.029	moderately benign-leaning
SaProt	LLR -6.83	tolerated
⇒ AlphaMissense, REVEL and SaProt all call this tolerated.
Splicing
SpliceAI	—	not looked up on this page · why
Pangolin	Δ0.36	gain · loss 0.00 · independent
Constraint at this position
Conservation	phyloP 8	GERP 0.76, phastCons 1
Regional constraint	o/e 0.51	unconstrained · MANE · 772 bp · p 0.00019 · regional, not allelic
Overall
CADD	20.6	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 0.00017% European (non-Finnish) · 2/1,178,086 alleles

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

Overall 0.000124% 2/1,609,416 alleles · very rare exomes 2/1,458,184 · genomes 0/151,232 · 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: RECQL
Protein: p.Ala641Val
Coding: c.1922C>T
MANE Select: NM_002907
dbSNP: rs1942902579
Type: single nucleotide variant
Location: chr12:21470222 (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-ala641val (accessed [today's date]).

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