Is BEST2 p.Pro385Ser (c.1153C>T) pathogenic?

BEST2 p.Pro385Ser (c.1153C>T) is classified Uncertain significance in BEST2 (ClinVar, Single submitter, 1 submitter; last evaluated 2024-03-19). AlphaMissense: likely benign (0.0801); Very rare (popmax 0.00547%, afr).

How common is BEST2 p.Pro385Ser (c.1153C>T) in the general population?

BEST2 p.Pro385Ser (c.1153C>T) is very rare (popmax 0.00547%, afr) (gnomAD).

What do computational predictors say about BEST2 p.Pro385Ser (c.1153C>T)?

AlphaMissense predicts likely benign (score 0.0801) — an in-silico prediction, not a clinical call.

BEST2 p.Pro385Ser

c.1153C>T · VCV3260806

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.0801 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 0.00547%, afr)

Missense predictors

0/3 damaging

AlphaMissense, REVEL, SaProt

Computational evidence

Protein change
AlphaMissense	0.0801	likely benign
REVEL	0.267	benign-leaning
SaProt	LLR -6.46	tolerated
⇒ AlphaMissense, REVEL and SaProt all call this tolerated.
Splicing
SpliceAI	<0.2	no splice effect predicted · four deltas, not one · how we know
Constraint at this position
Conservation	phyloP 2.6	GERP 0.26, phastCons 0.83
Regional constraint	o/e 1.04	unconstrained · MANE · 2,154 bp · p 0.5 · regional, not allelic
Overall
CADD	15.63	PHRED · no single calibrated threshold — expert panels disagree

ClinVar classifies this uncertain; the computational predictors unanimously lean tolerated — a triage signal, not a reclassification

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

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.00547% African / African-American · 4/73,178 alleles

Filtering AF 0.00178% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.00106%

Overall 0.000323% 5/1,546,364 alleles · very rare exomes 0/1,394,000 · genomes 5/152,364 · joint denominator

Ancestry group	Frequency	1 in
African / African-Americangrpmax	0.00547%	18,295
East Asian	0.00243%	41,200

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: BEST2
Protein: p.Pro385Ser
Coding: c.1153C>T
MANE Select: NM_017682
Type: single nucleotide variant
Location: chr19:12757700 (GRCh38)
Gene constraint: LOEUF 0.966 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 82.03 · 10 PDB

Full BEST2 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Similar variants

BEST2 p.Pro385Leu Uncertain significance ★ ⚠ same residue
BEST2 p.Ala105Val Uncertain significance ★ ⚠ same type
BEST2 p.Ala12Thr Uncertain significance ★ ⚠ same type
BEST2 p.Ala136Thr Uncertain significance ★ ⚠ same type
BEST2 p.Ala160Gly Uncertain significance ★ ⚠ same type
BEST2 p.Ala285Thr Uncertain significance ★ ⚠ same type
BEST2 p.Ala341Asp Uncertain significance ★ ⚠ same type
BEST2 p.Ala341Thr 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/best2-p-pro385ser (accessed [today's date]).

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