Is BECN2 p.Leu272= (c.814T>C) pathogenic?

BECN2 p.Leu272= (c.814T>C) is classified Likely benign in BECN2 (ClinVar, Single submitter, 1 submitter; last evaluated 2022-10-01). Rare (popmax 0.156%, nfe).

How common is BECN2 p.Leu272= (c.814T>C) in the general population?

BECN2 p.Leu272= (c.814T>C) is rare (popmax 0.156%, nfe) (gnomAD).

BECN2 p.Leu272=

c.814T>C · rs191909829 · VCV2640210

Likely benign Single submitter

Classification

Likely benign

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

gnomAD v4.1

Rare

rare (popmax 0.156%, nfe)

Computational evidence

Protein change
Missense predictors do not apply to this variant type; conservation/SpliceAI carries the signal.
Splicing
SpliceAI	Δ0.24	donor loss, 2 bp away · masked 0 · deltas
Constraint at this position
Conservation	phyloP -7.7	GERP -3.8
Overall
CADD	0.652	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.156% European (non-Finnish) · 1,545/988,000 alleles

Filtering AF 0.15% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.147%

Overall 0.151% 1,855/1,231,742 alleles · rare

Ancestry group	Frequency	1 in
Ashkenazi Jewishnot grpmax-eligible	0.7%	143
Finnishnot grpmax-eligible	0.331%	302
European (non-Finnish)grpmax	0.156%	639
Remaining individualsnot grpmax-eligible	0.142%	704
Middle Eastern	0.0623%	1,605
African / African-American	0.017%	5,867
Admixed American	0.00844%	11,843

Ashkenazi Jewish 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: BECN2
Protein: p.Leu272=
Coding: c.814T>C
MANE Select: NM_001290693
dbSNP: rs191909829
Type: single nucleotide variant
Location: chr1:241958580 (GRCh38)
Gene constraint: LOEUF 1.528 · pLI 0.48 (gnomAD)
Structure: AlphaFold pLDDT 77.12 · 4 PDB

Full BECN2 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Similar variants

BECN2 p.Arg243Met Benign ★★ same type
BECN2 p.Glu158Lys Benign ★★ same type
BECN2 p.Ile103Met Benign ★★ same type
BECN2 p.Cys121Ter 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/becn2-p-leu272 (accessed [today's date]).

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