Is BECN1 p.Ser90Phe (c.269C>T) pathogenic?

BECN1 p.Ser90Phe (c.269C>T) is classified Uncertain significance in BECN1 (ClinVar, Single submitter, 1 submitter; last evaluated 2024-09-10). AlphaMissense: likely pathogenic (0.8992); Very rare (popmax 0.0011%, sas).

How common is BECN1 p.Ser90Phe (c.269C>T) in the general population?

BECN1 p.Ser90Phe (c.269C>T) is very rare (popmax 0.0011%, sas) (gnomAD).

What do computational predictors say about BECN1 p.Ser90Phe (c.269C>T)?

AlphaMissense predicts likely pathogenic (score 0.8992) — an in-silico prediction, not a clinical call.

BECN1 p.Ser90Phe

c.269C>T · VCV3480396

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely pathogenic

0.8992 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 0.0011%, sas)

Missense predictors

2/3 damaging

AlphaMissense, REVEL, SaProt

Computational evidence

Protein change
AlphaMissense	0.8992	likely pathogenic
REVEL	0.285	benign-leaning
SaProt	LLR -11.47	damaging
⇒ AlphaMissense and SaProt call this damaging; REVEL does not.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 12	GERP 2.5, phastCons 1
Regional constraint	o/e 0.76	unconstrained · MANE · 5,038 bp · p 0.0083 · regional, not allelic
Overall
CADD	32.0	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 0.0011% South Asian · 1/91,080 alleles

Overall 6.2e-05% 1/1,614,182 alleles · very rare exomes 1/1,461,878 · genomes 0/152,304 · joint denominator

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: BECN1
Protein: p.Ser90Phe
Coding: c.269C>T
MANE Select: NM_001313998
Type: single nucleotide variant
Location: chr17:42818869 (GRCh38)
Gene constraint: LOEUF 0.33 · pLI 1.00 (gnomAD)
Structure: AlphaFold pLDDT 77.37 · 33 PDB
Residue 90: a modified residue (phosphoserine; by ampk)

Full BECN1 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Similar variants

BECN1 c.980+9T>C Benign ★★ same type
BECN1 c.-2-2A>G Uncertain significance ★ same type
BECN1 p.Arg255His Uncertain significance ★ ⚠ same type
BECN1 p.Arg329Gln Uncertain significance ★ ⚠ same type
BECN1 p.Arg80Cys Uncertain significance ★ ⚠ same type
BECN1 p.Arg80Leu Uncertain significance ★ ⚠ same type
BECN1 p.Asn286Asp Uncertain significance ★ ⚠ same type
BECN1 p.Gln224Glu 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/becn1-p-ser90phe (accessed [today's date]).

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