Is BCHE p.Gly601fs (c.1802del) pathogenic?

BCHE p.Gly601fs (c.1802del) is classified Uncertain significance in BCHE (ClinVar, Single submitter, 1 submitter; last evaluated 2025-11-24). Ultra-rare (popmax 0.0979%, sas).

How common is BCHE p.Gly601fs (c.1802del) in the general population?

BCHE p.Gly601fs (c.1802del) is ultra-rare (popmax 0.0979%, sas) (gnomAD).

BCHE p.Gly601fs

c.1802del · rs535319263 · VCV1878252

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

Consequence

frameshift

predicted LoF

gnomAD v4.1

Rare

ultra-rare (popmax 0.0979%, sas)

Computational evidence

Protein change
Missense predictors do not apply to this variant type; conservation carries the signal.
Consequence	frameshift	predicted loss-of-function
NMD	escapes	premature termination codon in the last exon (4 of 4) — the truncated protein is likely expressed. PVS1 input, not an applied code
Splicing
SpliceAI	—	not assessed · substitutions only
Constraint at this position
Conservation	phyloP 2.5	GERP -5.5, phastCons 1
Overall
CADD	25.7	PHRED · no single calibrated threshold — expert panels disagree

Predicted loss-of-function is descriptive, not an applied PVS1 code.

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.0979% South Asian · 89/90,890 alleles

Filtering AF 0.0814% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.0754%

Overall 0.00658% 106/1,610,698 alleles · ultra-rare

Ancestry group	Frequency	1 in
South Asiangrpmax	0.0979%	1,021
Middle Eastern	0.0165%	6,046
Remaining individualsnot grpmax-eligible	0.00802%	12,469
African / African-American	0.00534%	18,738
Finnishnot grpmax-eligible	0.00157%	63,896
European (non-Finnish)	0.00051%	196,264

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: BCHE
Protein: p.Gly601fs
Coding: c.1802del
MANE Select: NM_000055
dbSNP: rs535319263
Type: Deletion
Location: chr3:165773389 (GRCh38)
Gene constraint: LOEUF 1.195 · pLI <0.01 · ClinGen HI gene assoc. with recessive phenotype (gnomAD)
Structure: AlphaFold pLDDT 93.30 · 111 PDB

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

Similar variants

BCHE p.Gly601Val Uncertain significance ★ ⚠ same residue
BCHE p.Asn173_Tyr174insTer Pathogenic/Likely pathogenic ★★ same type
BCHE p.Ile34fs Pathogenic ★★ same type
BCHE p.Pro387fs Likely pathogenic ★★ same type
BCHE p.Arg166fs Likely pathogenic ★ same type
BCHE p.Leu121fs Likely pathogenic ★ same type
BCHE p.Tyr265fs Likely pathogenic ★ same type
BCHE c.-8-6_-8-3del 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/bche-p-gly601fs (accessed [today's date]).

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