Is BEND2 p.Ser188Tyr (c.563C>A) pathogenic?

BEND2 p.Ser188Tyr (c.563C>A) is classified Uncertain significance in BEND2 (ClinVar, Single submitter, 1 submitter; last evaluated 2022-01-26). AlphaMissense: likely benign (0.1506); Absent from gnomAD v4.1.

How common is BEND2 p.Ser188Tyr (c.563C>A) in the general population?

BEND2 p.Ser188Tyr (c.563C>A) is absent from gnomAD v4.1 (gnomAD).

What do computational predictors say about BEND2 p.Ser188Tyr (c.563C>A)?

AlphaMissense predicts likely benign (score 0.1506) — an in-silico prediction, not a clinical call.

BEND2 p.Ser188Tyr

c.563C>A · rs12859329 · VCV2273349

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.1506 · ACMG-weighted

gnomAD v4.1

Absent

absent from gnomAD v4.1

Missense predictors

0/3 damaging

AlphaMissense, REVEL, SaProt

Computational evidence

Protein change
AlphaMissense	0.1506	likely benign
REVEL	0.073	moderately benign-leaning
SaProt	LLR -8.42	tolerated
⇒ AlphaMissense, REVEL and SaProt all call this tolerated.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 0.26	GERP 1
Regional constraint	o/e 1.00	unconstrained · MANE · 50 kb · p 0.98 · regional, not allelic
Overall
CADD	15.32	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

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: BEND2
Protein: p.Ser188Tyr
Coding: c.563C>A
MANE Select: NM_153346
dbSNP: rs12859329
Type: single nucleotide variant
Location: chrX:18203845 (GRCh38)
Structure: AlphaFold pLDDT 49.94
Residue 188: a UniProt-annotated variant site (in)

Full BEND2 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Similar variants

BEND2 p.Gln198His Benign ★★ same type
BEND2 p.Gly580Val Benign ★★ same type
BEND2 p.Ser183Ile Benign ★★ ⚠ same type
BEND2 p.Thr367= Likely benign ★★ same type
BEND2 p.Val261Gly Benign ★★ same type
BEND2 p.Ala185Gly Uncertain significance ★ ⚠ same type
BEND2 p.Ala193Thr Uncertain significance ★ ⚠ same type
BEND2 p.Ala222Ser 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/bend2-p-ser188tyr (accessed [today's date]).

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