Is HBB p.Lys60= (c.180G>A) pathogenic?

HBB p.Lys60= (c.180G>A) is classified Likely benign in HBB (ClinVar, Multiple submitters, 5 submitters; last evaluated 2025-12-26). Ultra-rare (popmax 0.066%, mid); Associated with Inborn genetic diseases.

What condition is associated with HBB p.Lys60= (c.180G>A)?

HBB p.Lys60= (c.180G>A) is associated with Inborn genetic diseases, beta thalassemia (ClinVar).

How common is HBB p.Lys60= (c.180G>A) in the general population?

HBB p.Lys60= (c.180G>A) is ultra-rare (popmax 0.066%, mid) (gnomAD).

HBB p.Lys60=

c.180G>A · rs34621955 · VCV439139

Likely benign Multiple submitters

Classification

Likely benign

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 5 submitters

gnomAD v4.1

Rare

ultra-rare (popmax 0.066%, mid)

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 -6.4	GERP -3.7
Overall
CADD	3.86	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.066% Middle Eastern · 4/6,062 alleles

Filtering AF 0.0331% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.0293%

Overall 0.00694% 112/1,614,128 alleles · ultra-rare exomes 105/1,461,878 · genomes 7/152,250 · joint denominator

Ancestry group	Frequency	1 in
Middle Easterngrpmax	0.066%	1,516
South Asian	0.0439%	2,277
Remaining individualsnot grpmax-eligible	0.0128%	7,813
Admixed American	0.005%	20,008
European (non-Finnish)	0.00483%	20,702

Rarity supports pathogenicity (ACMG PM2); frequency above a disease-specific BA1/BS1 threshold argues against it. A variant frequent in one ancestry group can be near-absent in others, so a single global figure can mislead.

Variant & gene context

Gene: HBB
Protein: p.Lys60=
Coding: c.180G>A
MANE Select: NM_000518
dbSNP: rs34621955
Type: single nucleotide variant
Location: chr11:5226712 (GRCh38)
Gene constraint: LOEUF 1.964 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 97.09 · 350 PDB
Residue 60: a UniProt-annotated variant site (in i-high wycombe); a functional site (not glycated); an α-helix; a modified residue (n6-acetyllysine); 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

Also linked: beta thalassemia

Similar variants

HBB p.Lys60Asn Uncertain significance ★★ ⚠ same residue
HBB p.Lys60Thr Uncertain significance ★★ ⚠ same residue
HBB p.Lys60Ter Pathogenic same residue
HBB p.Lys60fs Pathogenic same residue
HBB c.316-146T>G Pathogenic ★★★ same condition
HBB c.316-197C>T Pathogenic ★★★ same condition
HBB c.92+5G>C Pathogenic ★★★ same condition
HBB c.-78A>C Pathogenic ★★★ 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-lys60 (accessed [today's date]).

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