Is BEST1 p.Phe84Val (c.250T>G) pathogenic?

BEST1 p.Phe84Val (c.250T>G) is classified Conflicting classifications of pathogenicity in BEST1 (ClinVar, Conflicting submitters, 2 submitters; last evaluated 2025-10-14). AlphaMissense: likely pathogenic (0.9888); Absent from gnomAD v4.1; Associated with BEST1-related disorder.

What condition is associated with BEST1 p.Phe84Val (c.250T>G)?

BEST1 p.Phe84Val (c.250T>G) is associated with BEST1-related disorder (ClinVar).

How common is BEST1 p.Phe84Val (c.250T>G) in the general population?

BEST1 p.Phe84Val (c.250T>G) is absent from gnomAD v4.1 (gnomAD).

What do computational predictors say about BEST1 p.Phe84Val (c.250T>G)?

AlphaMissense predicts likely pathogenic (score 0.9888) — an in-silico prediction, not a clinical call.

BEST1 p.Phe84Val

c.250T>G · VCV4709838

Conflicting classifications of pathogenicity Conflicting submitters

Classification

Conflicting classifications of pathogenicity

ClinVar

Review

Conflicting submitters ★☆☆☆

ClinVar · 2 submitters

AlphaMissense

likely pathogenic

0.9888 · ACMG-weighted

gnomAD v4.1

Not reported

no allele count reported in gnomAD v4.1 (AN 1,512,630)

Missense predictors

3/3 damaging

AlphaMissense, REVEL, SaProt

Conditions

BEST1-related disorder

Computational evidence

Protein change
AlphaMissense	0.9888	likely pathogenic · top 5% in BEST1
REVEL	0.983	strongly pathogenic-leaning
SaProt	LLR -14.80	damaging
⇒ AlphaMissense, REVEL and SaProt all call this damaging.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 4.8	GERP 2.4, phastCons 1
Regional constraint	o/e 0.91	unconstrained · MANE · 12 kb · p 0.011 · regional, not allelic
Overall
CADD	31.0	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

No allele count reported in gnomAD v4.1 (AN 1,512,630). This is missing data, not an absence: the variant may or may not be present in gnomAD. Rarity (ACMG PM2) and BA1/BS1 cannot be assessed for it.

Variant & gene context

Gene: BEST1
Protein: p.Phe84Val
Coding: c.250T>G
MANE Select: NM_004183
Type: single nucleotide variant
Location: chr11:61955720 (GRCh38)
Gene constraint: LOEUF 1.28 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 72.46 · 19 PDB
Residue 84: an α-helix

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

Disease context

BEST1-related disorder — disease report on Sugi Atlas → Associated genes, phenotypes, clinical trials & treatments

Similar variants

BEST1 c.636+1G>A Pathogenic ★★ same condition
BEST1 p.Ala10Val Pathogenic ★★ same condition
BEST1 p.Arg105Ser Pathogenic/Likely pathogenic ★★ same condition
BEST1 p.Arg130Ser Pathogenic/Likely pathogenic ★★ same condition
BEST1 p.Arg13Cys Pathogenic/Likely pathogenic ★★ ⚠ same condition
BEST1 p.Arg141Ser Pathogenic ★★ same condition
BEST1 p.Arg200Ter Pathogenic ★★ same condition
BEST1 p.Arg202Gln Likely pathogenic ★★ ⚠ same condition

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-phe84val (accessed [today's date]).

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