Is HBB p.Asn58= (c.174C>T) pathogenic?

HBB p.Asn58= (c.174C>T) is classified Likely benign in HBB (ClinVar, Multiple submitters, 3 submitters; last evaluated 2024-02-08). Very rare (popmax 0.000558%).

How common is HBB p.Asn58= (c.174C>T) in the general population?

HBB p.Asn58= (c.174C>T) is very rare (popmax 0.000558%) (gnomAD).

HBB p.Asn58=

c.174C>T · rs35278874 · VCV439138

Likely benign Multiple submitters

Classification

Likely benign

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 3 submitters

gnomAD v4.1

Rare

very rare (popmax 0.000558%)

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 -8.2	GERP -3.7
Overall
CADD	0.54	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.000558%

Overall 0.000558% 9/1,613,978 alleles · very rare exomes 8/1,461,872 · genomes 1/152,106 · joint denominator

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.Asn58=
Coding: c.174C>T
MANE Select: NM_000518
dbSNP: rs35278874
Type: single nucleotide variant
Location: chr11:5226718 (GRCh38)
Gene constraint: LOEUF 1.964 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 97.09 · 350 PDB
Residue 58: a UniProt-annotated variant site (in g-ferrara; unstable); a functional site ((microbial infection) cleavage; by n.americanus apr-2); the globin domain

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

Similar variants

HBB p.Asn58Lys Uncertain significance ★★ ⚠ 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
HBB p.Ala28Ser Pathogenic ★★★ ⚠ same type
HBB p.Lys18Ter 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-asn58 (accessed [today's date]).

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