Is BEST2 p.Arg120Ser (c.358C>A) pathogenic?

BEST2 p.Arg120Ser (c.358C>A) is classified Uncertain significance in BEST2 (ClinVar, Single submitter, 1 submitter; last evaluated 2025-05-15). AlphaMissense: ambiguous (0.436); Absent from gnomAD v4.1.

How common is BEST2 p.Arg120Ser (c.358C>A) in the general population?

BEST2 p.Arg120Ser (c.358C>A) is absent from gnomAD v4.1 (gnomAD).

What do computational predictors say about BEST2 p.Arg120Ser (c.358C>A)?

AlphaMissense predicts ambiguous (score 0.436) — an in-silico prediction, not a clinical call.

BEST2 p.Arg120Ser

c.358C>A · VCV3991315

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

ambiguous

0.436 · ACMG-weighted

gnomAD v4.1

Not reported

no allele count reported in gnomAD v4.1 (AN 1,560,136)

Computational evidence

Protein change
AlphaMissense	0.436	ambiguous
REVEL	0.642	indeterminate
SaProt	LLR -10.75	damaging
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 2.7	GERP 0.73, phastCons 1
Regional constraint	o/e 0.93	unconstrained · MANE · 3,147 bp · p 0.19 · regional, not allelic
Overall
CADD	23.0	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 1,560,136). 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: BEST2
Protein: p.Arg120Ser
Coding: c.358C>A
MANE Select: NM_017682
Type: single nucleotide variant
Location: chr19:12754662 (GRCh38)
Gene constraint: LOEUF 0.966 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 82.03 · 10 PDB
Residue 120: an α-helix

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

Similar variants

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
BEST2 p.Ala343Thr 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-arg120ser (accessed [today's date]).

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