Is BEST1 p.Ser16Phe (c.47C>T) pathogenic?

BEST1 p.Ser16Phe (c.47C>T) is classified Pathogenic in BEST1 (ClinVar, Single submitter, 2 submitters; last evaluated 2025-06-27). AlphaMissense: likely pathogenic (0.6116); Absent from gnomAD v4.1.

How common is BEST1 p.Ser16Phe (c.47C>T) in the general population?

BEST1 p.Ser16Phe (c.47C>T) is absent from gnomAD v4.1 (gnomAD).

What do computational predictors say about BEST1 p.Ser16Phe (c.47C>T)?

AlphaMissense predicts likely pathogenic (score 0.6116) — an in-silico prediction, not a clinical call.

BEST1 p.Ser16Phe

c.47C>T · rs281865210 · VCV99723

Pathogenic Single submitter

Classification

Pathogenic

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 2 submitters

AlphaMissense

likely pathogenic

0.6116 · ACMG-weighted

gnomAD v4.1

Absent

absent from gnomAD v4.1

Missense predictors

3/3 damaging

AlphaMissense, REVEL, SaProt

Computational evidence

Protein change
AlphaMissense	0.6116	likely pathogenic ✓ concordant with ClinVar
REVEL	0.857	moderately pathogenic-leaning
SaProt	LLR -10.00	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 2	GERP -4.8, phastCons 1
Regional constraint	o/e 0.91	unconstrained · MANE · 12 kb · p 0.011 · regional, not allelic
Overall
CADD	24.7	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.Ser16Phe
Coding: c.47C>T
MANE Select: NM_004183
dbSNP: rs281865210
Type: single nucleotide variant
Location: chr11:61951853 (GRCh38)
Gene constraint: LOEUF 1.28 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 72.46 · 19 PDB
Residue 16: an α-helix; 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.Ser16Pro Likely pathogenic ★ same residue
BEST1 p.Ser16Tyr 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-ser16phe (accessed [today's date]).

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