Is BEND5 p.Gly345= (c.1035C>T) pathogenic?

BEND5 p.Gly345= (c.1035C>T) is classified Likely benign in BEND5 (ClinVar, Single submitter, 1 submitter; last evaluated 2023-03-01). Rare (popmax 0.477%, nfe).

How common is BEND5 p.Gly345= (c.1035C>T) in the general population?

BEND5 p.Gly345= (c.1035C>T) is rare (popmax 0.477%, nfe) (gnomAD).

BEND5 p.Gly345=

c.1035C>T · rs114450193 · VCV2638810

Likely benign Single submitter

Classification

Likely benign

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

gnomAD v4.1

Rare

rare (popmax 0.477%, nfe)

Computational evidence

Protein change
Missense predictors do not apply to this variant type; conservation carries the signal.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 1.5	GERP 1.4, phastCons 1
Overall
CADD	13.11	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.477% European (non-Finnish) · 5,627/1,179,974 alleles

Filtering AF 0.466% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.462%

Overall 0.378% 6,099/1,614,010 alleles · rare

Ancestry group	Frequency	1 in
Amishnot grpmax-eligible	0.548%	182
European (non-Finnish)grpmax	0.477%	210
Admixed American	0.278%	359
Remaining individualsnot grpmax-eligible	0.25%	401
Finnishnot grpmax-eligible	0.105%	955
African / African-American	0.076%	1,316
Middle Eastern	0.0495%	2,021
East Asian	0.0134%	7,479
South Asian	0.011%	9,108
Ashkenazi Jewishnot grpmax-eligible	0.00338%	29,606

Amish shows a higher raw frequency than the grpmax group above it. gnomAD excludes bottlenecked groups — Finnish, Ashkenazi Jewish, Amish and “Remaining individuals” — from grpmax, because founder effects make their frequencies unrepresentative for filtering. The table is sorted by frequency, so an excluded group can sit above the grpmax row.

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.Gly345=
Coding: c.1035C>T
MANE Select: NM_024603
dbSNP: rs114450193
Type: single nucleotide variant
Location: chr1:48736312 (GRCh38)
Gene constraint: LOEUF 0.755 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 74.20
Residue 345: the ben domain

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-gly345 (accessed [today's date]).

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