Is HBB p.Lys18= (c.54G>A) pathogenic?

HBB p.Lys18= (c.54G>A) is classified Likely benign in HBB (ClinVar, Single submitter, 1 submitter; last evaluated 2023-04-30). No allele count reported in gnomAD v4.1 (AN 1,613,988).

How common is HBB p.Lys18= (c.54G>A) in the general population?

HBB p.Lys18= (c.54G>A) is no allele count reported in gnomAD v4.1 (AN 1,613,988) (gnomAD).

HBB p.Lys18=

c.54G>A · rs36006214 · VCV1538061

Likely benign Single submitter

Classification

Likely benign

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

gnomAD v4.1

Not reported

no allele count reported in gnomAD v4.1 (AN 1,613,988)

Computational evidence

Protein change
Missense predictors do not apply to this variant type; conservation carries the signal.
Splicing
SpliceAI	<0.2	no splice effect predicted · four deltas, not one · how we know
Constraint at this position
Conservation	phyloP -0.4	GERP -2.8, phastCons 0.061
Overall
CADD	8.678	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

No allele count reported in gnomAD v4.1 (AN 1,613,988). 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: HBB
Protein: p.Lys18=
Coding: c.54G>A
MANE Select: NM_000518
dbSNP: rs36006214
Type: single nucleotide variant
Location: chr11:5226968 (GRCh38)
Gene constraint: LOEUF 1.964 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 97.09 · 350 PDB
Residue 18: the globin domain; a UniProt-annotated variant site (in nagasaki); a UniProt-annotated variant site (in j-amiens); a UniProt-annotated variant site (in nikosia)

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

Similar variants

HBB p.Lys18Ter Pathogenic ★★★ same residue
HBB p.Lys18fs Pathogenic ★★ same residue
HBB p.Lys18_Val19insTer 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-lys18 (accessed [today's date]).

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