Is HBB p.Asp53= (c.159T>C) pathogenic?

HBB p.Asp53= (c.159T>C) is classified Likely benign in HBB (ClinVar, Single submitter, 1 submitter; last evaluated 2021-04-27). Very rare (popmax 0.00267%, afr).

How common is HBB p.Asp53= (c.159T>C) in the general population?

HBB p.Asp53= (c.159T>C) is very rare (popmax 0.00267%, afr) (gnomAD).

HBB p.Asp53=

c.159T>C · rs777114006 · VCV1143503

Likely benign Single submitter

Classification

Likely benign

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

gnomAD v4.1

Rare

very rare (popmax 0.00267%, afr)

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 0.22	GERP -0.65, phastCons 0.001
Overall
CADD	8.316	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.00267% African / African-American · 2/74,896 alleles

Filtering AF 0.000443% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.000166%

Overall 0.000186% 3/1,614,018 alleles · very rare exomes 1/1,461,876 · genomes 2/152,142 · joint denominator

Ancestry group	Frequency	1 in
African / African-Americangrpmax	0.00267%	37,448
European (non-Finnish)	8.47e-05%	1,180,026

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.Asp53=
Coding: c.159T>C
MANE Select: NM_000518
dbSNP: rs777114006
Type: single nucleotide variant
Location: chr11:5226733 (GRCh38)
Gene constraint: LOEUF 1.964 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 97.09 · 350 PDB
Residue 53: a UniProt-annotated variant site (in ocho rios); a UniProt-annotated variant site (in summer hill); a functional site ((microbial infection) cleavage; by n.americanus apr-2); an α-helix; the globin domain

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

Similar variants

HBB p.Asp53His Uncertain significance ★★ ⚠ same residue
HBB p.Asp53Ala Uncertain significance ★ ⚠ same residue
HBB p.Asp53Asn Conflicting classifications of pathogenicity ★ ⚠ same residue
HBB p.Asp53fs 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

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-asp53 (accessed [today's date]).

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