Is BEST1 p.Glu306Gln (c.916G>C) pathogenic?

BEST1 p.Glu306Gln (c.916G>C) is classified Pathogenic in BEST1 (ClinVar, Single submitter, 1 submitter; last evaluated 2023-08-17). AlphaMissense: likely pathogenic (0.8244); Absent from gnomAD v4.1.

How common is BEST1 p.Glu306Gln (c.916G>C) in the general population?

BEST1 p.Glu306Gln (c.916G>C) is absent from gnomAD v4.1 (gnomAD).

What do computational predictors say about BEST1 p.Glu306Gln (c.916G>C)?

AlphaMissense predicts likely pathogenic (score 0.8244) — an in-silico prediction, not a clinical call.

BEST1 p.Glu306Gln

c.916G>C · rs2134453498 · VCV1482656

Pathogenic Single submitter

Classification

Pathogenic

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely pathogenic

0.8244 · ACMG-weighted

gnomAD v4.1

Absent

absent from gnomAD v4.1

Missense predictors

3/3 damaging

AlphaMissense, REVEL, SaProt

Computational evidence

Protein change
AlphaMissense	0.8244	likely pathogenic ✓ concordant with ClinVar
REVEL	0.966	strongly pathogenic-leaning
SaProt	LLR -13.76	damaging
⇒ AlphaMissense, REVEL and SaProt all call this damaging.
Splicing
SpliceAI	<0.2	all four deltas below 0.2 · G>T here scores Δ0.20 · evaluated, not missing
Constraint at this position
Conservation	phyloP 9.6	GERP 2.2, phastCons 1
Regional constraint	o/e 0.91	unconstrained · MANE · 12 kb · p 0.011 · regional, not allelic
Overall
CADD	28.2	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

Absent from gnomAD v4.1. Not observed in any sequenced alleles — a rarity signal (ACMG PM2-supporting), not evidence of pathogenicity on its own.

Variant & gene context

Gene: BEST1
Protein: p.Glu306Gln
Coding: c.916G>C
MANE Select: NM_004183
dbSNP: rs2134453498
Type: single nucleotide variant
Location: chr11:61959546 (GRCh38)
Gene constraint: LOEUF 1.28 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 72.46 · 19 PDB
Residue 306: a UniProt-annotated variant site (in vmd2)

Full BEST1 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Similar variants

BEST1 p.Glu306Asp Pathogenic ★ same residue
BEST1 p.Glu306Gly Pathogenic ★ same residue
BEST1 c.1100+1G>C Pathogenic/Likely pathogenic ★★ same type
BEST1 c.1101-1G>C Likely pathogenic ★★ same type
BEST1 c.636+1G>A Pathogenic ★★ same type
BEST1 c.867+97G>A Pathogenic/Likely pathogenic ★★ same type
BEST1 p.Ala10Thr Pathogenic ★★ same type
BEST1 p.Ala10Val Pathogenic ★★ 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/best1-p-glu306gln (accessed [today's date]).

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