Is HBB p.Ser50= (c.150C>A) pathogenic?

HBB p.Ser50= (c.150C>A) is classified Likely benign in HBB (ClinVar, Single submitter, 1 submitter; last evaluated 2019-05-16). Absent from gnomAD v4.1.

How common is HBB p.Ser50= (c.150C>A) in the general population?

HBB p.Ser50= (c.150C>A) is absent from gnomAD v4.1 (gnomAD).

HBB p.Ser50=

c.150C>A · rs2133588564 · VCV1153698

Likely benign Single submitter

Classification

Likely benign

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

gnomAD v4.1

Absent

absent from gnomAD v4.1

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 0.045	GERP 1
Overall
CADD	6.87	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.Ser50=
Coding: c.150C>A
MANE Select: NM_000518
dbSNP: rs2133588564
Type: single nucleotide variant
Location: chr11:5226742 (GRCh38)
Gene constraint: LOEUF 1.964 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 97.09 · 350 PDB
Residue 50: a UniProt-annotated variant site (in las palmas; slightly unstable); the globin domain

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

Similar variants

HBB p.Ser50Phe Uncertain significance ★★ ⚠ same residue
HBB p.Ser50Cys Conflicting classifications of pathogenicity ★ ⚠ same residue
HBB p.Ser50fs Likely pathogenic same residue
HBB c.316-146T>G Pathogenic ★★★ same type
HBB c.316-197C>T Pathogenic ★★★ same type
HBB c.92+5G>C Pathogenic ★★★ same type
HBB c.-78A>C Pathogenic ★★★ same type
HBB c.*111A>G Pathogenic ★★★ 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/hbb-p-ser50 (accessed [today's date]).

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