Is DLEU7 p.Arg58Gln (c.173G>A) pathogenic?

DLEU7 p.Arg58Gln (c.173G>A) is classified Uncertain significance in DLEU7 (ClinVar, Single submitter, 1 submitter; last evaluated 2024-08-28). AlphaMissense: likely benign (0.108); Rare (popmax 0.886%, mid).

How common is DLEU7 p.Arg58Gln (c.173G>A) in the general population?

DLEU7 p.Arg58Gln (c.173G>A) is rare (popmax 0.886%, mid) (gnomAD).

What do computational predictors say about DLEU7 p.Arg58Gln (c.173G>A)?

AlphaMissense predicts likely benign (score 0.108) — an in-silico prediction, not a clinical call.

DLEU7 p.Arg58Gln

c.173G>A · rs142725081 · VCV2215176

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.108 · ACMG-weighted

gnomAD v4.1

Rare

rare (popmax 0.886%, mid)

Missense predictors

0/3 damaging

AlphaMissense, REVEL, SaProt

Computational evidence

Protein change
AlphaMissense	0.108	likely benign
REVEL	0.029	moderately benign-leaning
SaProt	LLR -7.71	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 -0.016	GERP 0.13
Regional constraint	o/e 0.98	unconstrained · MANE · 20 kb · p 0.7 · regional, not allelic
Overall
CADD	15.23	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 0.886% Middle Eastern · 32/3,612 alleles

Filtering AF 0.645% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.563%

Overall 0.037% 492/1,330,460 alleles · rare

Ancestry group	Frequency	1 in
Middle Easterngrpmax	0.886%	113
Ashkenazi Jewishnot grpmax-eligible	0.335%	298
Remaining individualsnot grpmax-eligible	0.107%	938
Admixed American	0.0921%	1,086
African / African-American	0.0418%	2,394
South Asian	0.0277%	3,612
European (non-Finnish)	0.0264%	3,784
East Asian	0.00313%	31,926

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: DLEU7
Protein: p.Arg58Gln
Coding: c.173G>A
MANE Select: NM_001306135
dbSNP: rs142725081
Type: single nucleotide variant
Location: chr13:50843474 (GRCh38)
Gene constraint: LOEUF 1.902 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 75.45
Residue 58: the 'disordered' region

Full DLEU7 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Similar variants

DLEU7 p.Ala2Val Uncertain significance ★ ⚠ same type
DLEU7 p.Ala49Thr Uncertain significance ★ ⚠ same type
DLEU7 p.Ala51Thr Uncertain significance ★ ⚠ same type
DLEU7 p.Ala80Thr Uncertain significance ★ ⚠ same type
DLEU7 p.Ala83Pro Uncertain significance ★ ⚠ same type
DLEU7 p.Ala9Ser Uncertain significance ★ ⚠ same type
DLEU7 p.Arg123Gly Uncertain significance ★ ⚠ same type
DLEU7 p.Arg52Ser 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/dleu7-p-arg58gln (accessed [today's date]).

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