Is HBB p.Ser45= (c.135C>G) pathogenic?

HBB p.Ser45= (c.135C>G) is classified Likely benign in HBB (ClinVar, Single submitter, 1 submitter; last evaluated 2019-08-12). Absent from gnomAD v4.1; Associated with Inborn genetic diseases.

What condition is associated with HBB p.Ser45= (c.135C>G)?

HBB p.Ser45= (c.135C>G) is associated with Inborn genetic diseases (ClinVar).

How common is HBB p.Ser45= (c.135C>G) in the general population?

HBB p.Ser45= (c.135C>G) is absent from gnomAD v4.1 (gnomAD).

HBB p.Ser45=

c.135C>G · rs2494296012 · VCV1770789

Likely benign Single submitter

Classification

Likely benign

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

gnomAD v4.1

Absent

absent from gnomAD v4.1

Conditions

Inborn genetic diseases

Computational evidence

Protein change
Missense predictors do not apply to this variant type; conservation carries the signal.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP -0.33	GERP 1
Overall
CADD	10.5	PHRED · no single calibrated threshold — expert panels disagree

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: HBB
Protein: p.Ser45=
Coding: c.135C>G
MANE Select: NM_000518
dbSNP: rs2494296012
Type: single nucleotide variant
Location: chr11:5226757 (GRCh38)
Gene constraint: LOEUF 1.964 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 97.09 · 350 PDB
Residue 45: a UniProt-annotated variant site (in mississippi); an α-helix; a modified residue (phosphoserine); the globin domain

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

Disease context

Inborn genetic diseases — disease report on Sugi Atlas → Associated genes, phenotypes, clinical trials & treatments

Similar variants

HBB p.Ser45Cys Uncertain significance ★★ ⚠ same residue
HBB p.His64Tyr Pathogenic/Likely pathogenic ★★ same condition
HBB p.His144= Benign/Likely benign ★★ same condition
HBB p.Leu82= Likely benign ★★ same condition
HBB p.Lys60= Likely benign ★★ same condition
HBB p.Val55= Likely benign ★★ same condition
HBB p.Ala11= Conflicting classifications of pathogenicity ★ same condition
HBB p.Val134= Conflicting classifications of pathogenicity ★ same condition

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/hbb-p-ser45 (accessed [today's date]).

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