Is HSPB2 p.Arg4Ser (c.10C>A) pathogenic?

HSPB2 p.Arg4Ser (c.10C>A) is classified Uncertain significance in HSPB2 (ClinVar, Single submitter, 1 submitter; last evaluated 2023-04-10). AlphaMissense: ambiguous (0.451); Absent from gnomAD v4.1.

How common is HSPB2 p.Arg4Ser (c.10C>A) in the general population?

HSPB2 p.Arg4Ser (c.10C>A) is absent from gnomAD v4.1 (gnomAD).

What do computational predictors say about HSPB2 p.Arg4Ser (c.10C>A)?

AlphaMissense predicts ambiguous (score 0.451) — an in-silico prediction, not a clinical call.

HSPB2 p.Arg4Ser

c.10C>A · rs1965509144 · VCV2524688

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

ambiguous

0.451 · ACMG-weighted

gnomAD v4.1

Absent

absent from gnomAD v4.1

Missense predictors

1/2 damaging

REVEL, SaProt · AlphaMissense no call

Computational evidence

Protein change
AlphaMissense	0.451	ambiguous
REVEL	0.665	pathogenic-leaning
SaProt	LLR -6.05	tolerated
⇒ REVEL calls this damaging; SaProt does not; AlphaMissense makes no call.
Splicing
SpliceAI	—	not looked up on this page · why
Constraint at this position
Conservation	phyloP 7.4	GERP 2.1, phastCons 1
Regional constraint	o/e 1.00	unconstrained · MANE · 1,062 bp · p 0.99 · regional, not allelic
Overall
CADD	26.8	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: HSPB2
Protein: p.Arg4Ser
Coding: c.10C>A
MANE Select: NM_001289808 · reported on NM_001541
dbSNP: rs1965509144
Type: single nucleotide variant
Location: chr11:111912839 (GRCh38)

Full HSPB2 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

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/hspb2-p-arg4ser (accessed [today's date]).

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