Is RECQL p.Val86Ile (c.256G>A) pathogenic?

RECQL p.Val86Ile (c.256G>A) is classified Conflicting classifications of pathogenicity in RECQL (ClinVar, Conflicting submitters, 2 submitters; last evaluated 2024-10-04). AlphaMissense: likely benign (0.0701); Very rare (popmax 0.00223%, eas).

How common is RECQL p.Val86Ile (c.256G>A) in the general population?

RECQL p.Val86Ile (c.256G>A) is very rare (popmax 0.00223%, eas) (gnomAD).

What do computational predictors say about RECQL p.Val86Ile (c.256G>A)?

AlphaMissense predicts likely benign (score 0.0701) — an in-silico prediction, not a clinical call.

RECQL p.Val86Ile

c.256G>A · rs996086612 · VCV1793225

Conflicting classifications of pathogenicity Conflicting submitters

Classification

Conflicting classifications of pathogenicity

ClinVar

Review

Conflicting submitters ★☆☆☆

ClinVar · 2 submitters

AlphaMissense

likely benign

0.0701 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 0.00223%, eas)

Missense predictors

0/3 damaging

AlphaMissense, REVEL, SaProt

Computational evidence

Protein change
AlphaMissense	0.0701	likely benign
REVEL	0.058	moderately benign-leaning
SaProt	LLR -7.77	tolerated
⇒ AlphaMissense, REVEL and SaProt all call this tolerated.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 0.23	GERP 0.87, phastCons 0.96
Regional constraint	o/e 0.94	unconstrained · MANE · 29 kb · p 0.095 · regional, not allelic
Overall
CADD	14.6	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 0.00223% East Asian · 1/44,774 alleles

Overall 6.2e-05% 1/1,612,326 alleles · very rare exomes 1/1,460,142 · genomes 0/152,184 · 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.Val86Ile
Coding: c.256G>A
MANE Select: NM_002907
dbSNP: rs996086612
Type: single nucleotide variant
Location: chr12:21490337 (GRCh38)
Gene constraint: LOEUF 1.235 · pLI <0.01 · ClinGen HI gene assoc. with recessive phenotype (gnomAD)
Structure: AlphaFold pLDDT 86.55 · 7 PDB

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

Similar variants

RECQL p.Val86Phe Uncertain significance ★★ ⚠ same residue
RECQL p.Val86Ala Uncertain significance ★ ⚠ same residue
RECQL p.Val86Asp Uncertain significance ★ ⚠ 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
RECQL c.1356-12A>G 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-val86ile (accessed [today's date]).

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