Is HBB p.Ala11= (c.33C>A) pathogenic?

HBB p.Ala11= (c.33C>A) is classified Conflicting classifications of pathogenicity in HBB (ClinVar, Conflicting submitters, 9 submitters; last evaluated 2025-05-28). Ultra-rare (popmax 0.0231%, sas); Associated with Inborn genetic diseases.

What condition is associated with HBB p.Ala11= (c.33C>A)?

HBB p.Ala11= (c.33C>A) is associated with Inborn genetic diseases, beta thalassemia (ClinVar).

How common is HBB p.Ala11= (c.33C>A) in the general population?

HBB p.Ala11= (c.33C>A) is ultra-rare (popmax 0.0231%, sas) (gnomAD).

HBB p.Ala11=

c.33C>A · rs35799536 · VCV439155

Conflicting classifications of pathogenicity Conflicting submitters

Classification

Conflicting classifications of pathogenicity

ClinVar

Review

Conflicting submitters ★☆☆☆

ClinVar · 9 submitters

gnomAD v4.1

Rare

ultra-rare (popmax 0.0231%, sas)

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 -20	GERP -3.7
Overall
CADD	0.04	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.0231% South Asian · 21/91,064 alleles

Filtering AF 0.0154% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.0129%

Overall 0.00143% 23/1,613,032 alleles · ultra-rare exomes 21/1,460,732 · genomes 2/152,300 · joint denominator

Ancestry group	Frequency	1 in
South Asiangrpmax	0.0231%	4,336
Remaining individualsnot grpmax-eligible	0.0032%	31,237

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.Ala11=
Coding: c.33C>A
MANE Select: NM_000518
dbSNP: rs35799536
Type: single nucleotide variant
Location: chr11:5226989 (GRCh38)
Gene constraint: LOEUF 1.964 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 97.09 · 350 PDB
Residue 11: an α-helix; the globin domain; a UniProt-annotated variant site (in ankara); a UniProt-annotated variant site (in iraq-halabja)

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.Ala11fs Pathogenic ★★ same residue
HBB p.Ala11Thr Conflicting classifications of pathogenicity ★ ⚠ 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
HBB c.*111A>G Pathogenic ★★★ same condition
HBB p.Ala28Ser 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-ala11 (accessed [today's date]).

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