Is DLEU7 p.Val46Met (c.136G>A) pathogenic?

DLEU7 p.Val46Met (c.136G>A) is classified Uncertain significance in DLEU7 (ClinVar, Single submitter, 1 submitter; last evaluated 2021-11-22). AlphaMissense: likely benign (0.1288); Very rare (popmax 0.00922%, eas).

How common is DLEU7 p.Val46Met (c.136G>A) in the general population?

DLEU7 p.Val46Met (c.136G>A) is very rare (popmax 0.00922%, eas) (gnomAD).

What do computational predictors say about DLEU7 p.Val46Met (c.136G>A)?

AlphaMissense predicts likely benign (score 0.1288) — an in-silico prediction, not a clinical call.

DLEU7 p.Val46Met

c.136G>A · rs778394562 · VCV2262057

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.1288 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 0.00922%, eas)

Missense predictors

0/3 damaging

AlphaMissense, REVEL, SaProt

Computational evidence

Protein change
AlphaMissense	0.1288	likely benign
REVEL	0.057	moderately benign-leaning
SaProt	LLR -7.98	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 0.5	GERP 3.1, phastCons 0.73
Regional constraint	o/e 0.98	unconstrained · MANE · 20 kb · p 0.7 · regional, not allelic
Overall
CADD	17.98	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 0.00922% East Asian · 3/32,530 alleles

Filtering AF 0.00244% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.00128%

Overall 0.00184% 26/1,409,790 alleles · very rare

Ancestry group	Frequency	1 in
East Asiangrpmax	0.00922%	10,843
Admixed American	0.00373%	26,774
African / African-American	0.00306%	32,703
Remaining individualsnot grpmax-eligible	0.00185%	54,112
European (non-Finnish)	0.00174%	57,519

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.Val46Met
Coding: c.136G>A
MANE Select: NM_001306135
dbSNP: rs778394562
Type: single nucleotide variant
Location: chr13:50843511 (GRCh38)
Gene constraint: LOEUF 1.902 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 75.45
Residue 46: 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-val46met (accessed [today's date]).

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