Is DLEU7 p.Leu157Pro (c.470T>C) pathogenic?

DLEU7 p.Leu157Pro (c.470T>C) is classified Uncertain significance in DLEU7 (ClinVar, Single submitter, 1 submitter; last evaluated 2022-10-27). Very rare (popmax 0.00111%, sas).

How common is DLEU7 p.Leu157Pro (c.470T>C) in the general population?

DLEU7 p.Leu157Pro (c.470T>C) is very rare (popmax 0.00111%, sas) (gnomAD).

DLEU7 p.Leu157Pro

c.470T>C · rs1376779234 · VCV2321287

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

gnomAD v4.1

Rare

very rare (popmax 0.00111%, sas)

Computational evidence

Protein change
Missense predictors do not apply to this variant type; conservation carries the signal.
REVEL	0.043	moderately benign-leaning
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP -0.2	GERP -3.8
Overall
CADD	3.034	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.00111% South Asian · 1/90,234 alleles

Overall 6.85e-05% 1/1,458,844 alleles · very rare

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.Leu157Pro
Coding: c.470T>C
MANE Select: NM_001306135 · reported on NM_198989
dbSNP: rs1376779234
Type: single nucleotide variant
Location: chr13:50713230 (GRCh38)
Gene constraint: LOEUF 1.902 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 75.45

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-leu157pro (accessed [today's date]).

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