Is RECQL p.Val136Ile (c.406G>A) pathogenic?

RECQL p.Val136Ile (c.406G>A) is classified Conflicting classifications of pathogenicity in RECQL (ClinVar, Conflicting submitters, 6 submitters; last evaluated 2025-07-21). AlphaMissense: likely benign (0.1387); Rare (popmax 0.163%, afr); Associated with Hereditary cancer.

What condition is associated with RECQL p.Val136Ile (c.406G>A)?

RECQL p.Val136Ile (c.406G>A) is associated with Hereditary cancer, RECON progeroid syndrome (ClinVar).

How common is RECQL p.Val136Ile (c.406G>A) in the general population?

RECQL p.Val136Ile (c.406G>A) is rare (popmax 0.163%, afr) (gnomAD).

What do computational predictors say about RECQL p.Val136Ile (c.406G>A)?

AlphaMissense predicts likely benign (score 0.1387) — an in-silico prediction, not a clinical call.

RECQL p.Val136Ile

c.406G>A · rs138278747 · VCV584820

Conflicting classifications of pathogenicity Conflicting submitters

Classification

Conflicting classifications of pathogenicity

ClinVar

Review

Conflicting submitters ★☆☆☆

ClinVar · 6 submitters

AlphaMissense

likely benign

0.1387 · ACMG-weighted

gnomAD v4.1

Rare

rare (popmax 0.163%, afr)

Missense predictors

0/2 damaging

AlphaMissense, SaProt · REVEL no call

Conditions

Hereditary cancer

Computational evidence

Protein change
AlphaMissense	0.1387	likely benign
REVEL	0.294	indeterminate
SaProt	LLR -9.94	tolerated
⇒ AlphaMissense and SaProt both call this tolerated; REVEL makes no call.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 4.8	GERP 1.9, phastCons 1
Regional constraint	o/e 0.94	unconstrained · MANE · 29 kb · p 0.095 · regional, not allelic
Overall
CADD	26.4	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 0.163% African / African-American · 109/66,928 alleles

Filtering AF 0.138% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.129%

Overall 0.00984% 153/1,555,656 alleles · rare

Ancestry group	Frequency	1 in
African / African-Americangrpmax	0.163%	614
Middle Eastern	0.0347%	2,882
East Asian	0.026%	3,848
Remaining individualsnot grpmax-eligible	0.015%	6,660
Admixed American	0.0097%	10,311
South Asian	0.00357%	27,973
European (non-Finnish)	0.00121%	82,701

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.Val136Ile
Coding: c.406G>A
MANE Select: NM_002907
dbSNP: rs138278747
Type: single nucleotide variant
Location: chr12:21486574 (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 136: the helicase atp-binding domain; a β-strand

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

Disease context

Hereditary cancer — disease report on Sugi Atlas → Associated genes, phenotypes, clinical trials & treatments

Also linked: RECON progeroid syndrome

Similar variants

RECQL p.Val136Ala Uncertain significance ★★ ⚠ same residue
RECQL p.Val136= Likely benign ★★ same residue
RECQL p.Val136Leu Uncertain significance ★ ⚠ same residue
RECQL p.Val136Phe Uncertain significance ★ ⚠ same residue
RECQL c.394+1G>A Uncertain significance ★★ same condition
RECQL c.867+3A>T Uncertain significance ★★ same condition
RECQL p.Ala459Ser Uncertain significance ★★ ⚠ same condition
RECQL p.Asp264Glu Uncertain significance ★★ ⚠ same condition

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-val136ile (accessed [today's date]).

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