Is BECN2 p.Ile103Met (c.309T>G) pathogenic?

BECN2 p.Ile103Met (c.309T>G) is classified Benign in BECN2 (ClinVar, Multiple submitters, 2 submitters; last evaluated 2018-07-24). AlphaMissense: likely benign (0.2288); Common (popmax 6.82%, mid) — too common for a highly-penetrant pathogenic allele.

What do computational predictors say about BECN2 p.Ile103Met (c.309T>G)?

AlphaMissense predicts likely benign (score 0.2288) — an in-silico prediction, not a clinical call.

BECN2 p.Ile103Met

Q: How common is BECN2 p.Ile103Met (c.309T>G) in the general population?

BECN2 p.Ile103Met (c.309T>G) is common (popmax 6.82%, mid) — too common for a highly-penetrant pathogenic allele (gnomAD).

c.309T>G · rs61736147 · VCV769259

Benign Multiple submitters

Classification

Benign

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 2 submitters

AlphaMissense

likely benign

0.2288 · ACMG-weighted

gnomAD v4.1

Common

common (popmax 6.82%, mid) — too common for a highly-penetrant pathogenic allele

Missense predictors

0/2 damaging

AlphaMissense, SaProt

Computational evidence

Protein change
AlphaMissense	0.2288	likely benign
SaProt	LLR -6.79	tolerated
⇒ AlphaMissense and SaProt both call this tolerated.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP -1.9	GERP -3.8
Regional constraint	o/e 0.84	unconstrained · MANE · 1,292 bp · p 0.00039 · regional, not allelic
Overall
CADD	15.83	PHRED · no single calibrated threshold — expert panels disagree

AlphaMissense carries the ACMG weight for missense; REVEL and SaProt are independent agreement signals.

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 6.82% Middle Eastern · 219/3,210 alleles

Filtering AF 6.42% ClinGen BA1/BS1 input FAF95, joint · FAF99 6.4%

Overall 5.83% 71,879/1,231,962 alleles · common

Ancestry group	Frequency	1 in
Middle Easterngrpmax	6.82%	15
European (non-Finnish)	6.46%	15
Finnishnot grpmax-eligible	6.42%	16
Remaining individualsnot grpmax-eligible	5.27%	19
Ashkenazi Jewishnot grpmax-eligible	4.81%	21
Admixed American	4.51%	22
Amishnot grpmax-eligible	2.74%	36
South Asian	2.61%	38
African / African-American	1.16%	87
East Asian	0.136%	737

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.Ile103Met
Coding: c.309T>G
MANE Select: NM_001290693
dbSNP: rs61736147
Type: single nucleotide variant
Location: chr1:241958075 (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.Cys121Ter Uncertain significance ★ same type
BECN2 p.Leu272= Likely benign ★ 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-ile103met (accessed [today's date]).

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