Is RECQL p.Val173Asp (c.518T>A) pathogenic?

RECQL p.Val173Asp (c.518T>A) is classified Conflicting classifications of pathogenicity in RECQL (ClinVar, Conflicting submitters, 6 submitters; last evaluated 2025-11-05). AlphaMissense: likely pathogenic (0.9833); Ultra-rare (popmax 0.0275%, sas); Associated with RECQL-related disorder.

What condition is associated with RECQL p.Val173Asp (c.518T>A)?

RECQL p.Val173Asp (c.518T>A) is associated with RECQL-related disorder, hereditary neoplastic syndrome (ClinVar).

How common is RECQL p.Val173Asp (c.518T>A) in the general population?

RECQL p.Val173Asp (c.518T>A) is ultra-rare (popmax 0.0275%, sas) (gnomAD).

What do computational predictors say about RECQL p.Val173Asp (c.518T>A)?

AlphaMissense predicts likely pathogenic (score 0.9833) — an in-silico prediction, not a clinical call.

RECQL p.Val173Asp

c.518T>A · rs144313838 · VCV584814

Conflicting classifications of pathogenicity Conflicting submitters

Classification

Conflicting classifications of pathogenicity

ClinVar

Review

Conflicting submitters ★☆☆☆

ClinVar · 6 submitters

AlphaMissense

likely pathogenic

0.9833 · ACMG-weighted

gnomAD v4.1

Rare

ultra-rare (popmax 0.0275%, sas)

Missense predictors

2/2 damaging

AlphaMissense, SaProt · REVEL indeterminate

Conditions

RECQL-related disorder

Computational evidence

Protein change
AlphaMissense	0.9833	likely pathogenic · top 8% in RECQL
REVEL	0.559	indeterminate
SaProt	LLR -15.99	damaging
⇒ AlphaMissense and SaProt both call this damaging; REVEL is indeterminate.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 11	GERP 1.5, phastCons 1
Regional constraint	o/e 0.94	unconstrained · MANE · 29 kb · p 0.095 · regional, not allelic
Overall
CADD	32.0	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 0.0275% South Asian · 23/83,650 alleles

Filtering AF 0.0188% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.0159%

Overall 0.0147% 231/1,576,312 alleles · ultra-rare exomes 205/1,424,168 · genomes 26/152,144 · joint denominator

Ancestry group	Frequency	1 in
Amishnot grpmax-eligible	0.329%	304
South Asiangrpmax	0.0275%	3,637
Remaining individualsnot grpmax-eligible	0.0164%	6,104
European (non-Finnish)	0.0159%	6,287
Finnishnot grpmax-eligible	0.011%	9,070
Admixed American	0.00208%	48,008
African / African-American	0.00139%	72,092

Amish shows a higher raw frequency than the grpmax group above it. gnomAD excludes bottlenecked groups — Finnish, Ashkenazi Jewish, Amish and “Remaining individuals” — from grpmax, because founder effects make their frequencies unrepresentative for filtering. The table is sorted by frequency, so an excluded group can sit above the grpmax row.

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.Val173Asp
Coding: c.518T>A
MANE Select: NM_002907
dbSNP: rs144313838
Type: single nucleotide variant
Location: chr12:21483558 (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 173: the helicase atp-binding domain; an α-helix

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

Disease context

RECQL-related disorder

Also linked: hereditary neoplastic syndrome

Similar variants

RECQL p.Val173Ala Uncertain significance ★ same residue
RECQL p.Val173Ile Uncertain significance ★ ⚠ same residue
RECQL c.1216+3A>G Uncertain significance ★★ same condition
RECQL c.867+3A>T Uncertain significance ★★ same condition
RECQL p.Arg407Ter Uncertain significance ★★ same condition
RECQL p.Cys447Arg Uncertain significance ★★ ⚠ same condition
RECQL p.Leu28Phe Uncertain significance ★★ ⚠ same condition
RECQL p.Leu550Gln 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-val173asp (accessed [today's date]).

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