Is BEND7 p.Leu370Arg (c.1109T>G) pathogenic?

BEND7 p.Leu370Arg (c.1109T>G) is classified Uncertain significance in BEND7 (ClinVar, Single submitter, 1 submitter; last evaluated 2025-01-07). Very rare (popmax 0.00331%, nfe).

How common is BEND7 p.Leu370Arg (c.1109T>G) in the general population?

BEND7 p.Leu370Arg (c.1109T>G) is very rare (popmax 0.00331%, nfe) (gnomAD).

BEND7 p.Leu370Arg

c.1109T>G · VCV3824183

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

gnomAD v4.1

Rare

very rare (popmax 0.00331%, nfe)

Computational evidence

Protein change
Missense predictors do not apply to this variant type; conservation carries the signal.
REVEL	0.163	moderately benign-leaning
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP -0.82	GERP -1.6
Overall
CADD	5.939	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.00331% European (non-Finnish) · 39/1,179,084 alleles

Filtering AF 0.00248% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.00217%

Overall 0.00254% 41/1,612,164 alleles · very rare

Ancestry group	Frequency	1 in
European (non-Finnish)grpmax	0.00331%	30,233
Remaining individualsnot grpmax-eligible	0.0032%	31,203

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: BEND7
Protein: p.Leu370Arg
Coding: c.1109T>G
MANE Select: NM_001369863 · reported on NM_152751
Type: single nucleotide variant
Location: chr10:13439470 (GRCh38)
Gene constraint: LOEUF 0.842 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 62.17
Residue 370: the ben domain

Full BEND7 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Similar variants

BEND7 p.Leu370Met Uncertain significance ★ same residue
BEND7 p.Ala103Val Uncertain significance ★ same type
BEND7 p.Ala105Asp Uncertain significance ★ same type
BEND7 p.Ala105Val Uncertain significance ★ same type
BEND7 p.Ala255Gly Uncertain significance ★ same type
BEND7 p.Ala397Val Uncertain significance ★ same type
BEND7 p.Arg114Cys Uncertain significance ★ same type
BEND7 p.Arg134Cys 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/bend7-p-leu370arg (accessed [today's date]).

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