Is BEND5 p.Leu8= (c.24G>A) pathogenic?

BEND5 p.Leu8= (c.24G>A) is classified Likely benign in BEND5 (ClinVar, Single submitter, 1 submitter; last evaluated 2024-09-26). Very rare (popmax 0.00741%, sas).

How common is BEND5 p.Leu8= (c.24G>A) in the general population?

BEND5 p.Leu8= (c.24G>A) is very rare (popmax 0.00741%, sas) (gnomAD).

BEND5 p.Leu8=

c.24G>A · VCV3480444

Likely benign Single submitter

Classification

Likely benign

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

gnomAD v4.1

Rare

very rare (popmax 0.00741%, sas)

Computational evidence

Protein change
Missense predictors do not apply to this variant type; conservation carries the signal.
Splicing
SpliceAI	—	not looked up on this page · why
Pangolin	Δ0.29	gain · loss 0.00 · independent
Constraint at this position
Conservation	phyloP 5.6	GERP 1.7, phastCons 1
Overall
CADD	15.54	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.00741% South Asian · 6/80,984 alleles

Filtering AF 0.00316% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.00214%

Overall 0.000584% 8/1,370,262 alleles · very rare

Ancestry group	Frequency	1 in
South Asiangrpmax	0.00741%	13,497
Remaining individualsnot grpmax-eligible	0.0017%	58,866
African / African-American	0.00144%	69,354

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: BEND5
Protein: p.Leu8=
Coding: c.24G>A
MANE Select: NM_032785 · reported on NM_024603
Type: single nucleotide variant
Location: chr1:48776808 (GRCh38)

Full BEND5 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

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/bend5-p-leu8 (accessed [today's date]).

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