Is HBD p.Lys121= (c.363G>A) pathogenic?

HBD p.Lys121= (c.363G>A) is classified Likely benign in HBD (ClinVar, No assertion criteria, 1 submitter; last evaluated 2019-07-15). Rare (popmax 0.14%, afr); Associated with HBD-related disorder.

What condition is associated with HBD p.Lys121= (c.363G>A)?

HBD p.Lys121= (c.363G>A) is associated with HBD-related disorder (ClinVar).

How common is HBD p.Lys121= (c.363G>A) in the general population?

HBD p.Lys121= (c.363G>A) is rare (popmax 0.14%, afr) (gnomAD).

HBD p.Lys121=

c.363G>A · rs148878316 · VCV3049559

Likely benign No assertion criteria

Classification

Likely benign

ClinVar

Review

No assertion criteria ☆☆☆☆

ClinVar · 1 submitter

gnomAD v4.1

Rare

rare (popmax 0.14%, afr)

Conditions

HBD-related disorder

Computational evidence

Protein change
Missense predictors do not apply to this variant type; conservation carries the signal.
REVEL	0.073	moderately benign-leaning
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP -8.9	GERP -1
Overall
CADD	0.791	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.14% African / African-American · 105/75,022 alleles

Filtering AF 0.118% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.11%

Overall 0.0083% 134/1,614,030 alleles · rare exomes 79/1,461,756 · genomes 55/152,274 · joint denominator

Ancestry group	Frequency	1 in
African / African-Americangrpmax	0.14%	714
Remaining individualsnot grpmax-eligible	0.0304%	3,289
Admixed American	0.00333%	30,000
South Asian	0.00329%	30,353
European (non-Finnish)	0.000424%	235,993

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: HBD
Protein: p.Lys121=
Coding: c.363G>A
MANE Select: NM_000519
dbSNP: rs148878316
Type: single nucleotide variant
Location: chr11:5233045 (GRCh38)
Gene constraint: LOEUF 1.586 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 96.81 · 2 PDB
Residue 121: the globin domain; an α-helix

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

Disease context

HBD-related disorder

Similar variants

HBD c.*102G>A Uncertain significance ★ same condition
HBD p.Gly75= Uncertain significance ★★ same type
HBD p.Thr5Ile Uncertain significance ★★ ⚠ same type
HBD c.315+146T>G Benign ★★ same type
HBD p.His98= Benign ★★ same type
HBD c.316-2A>G Pathogenic ★ same type
HBD p.Gly137Asp Pathogenic ★ ⚠ same type
HBD c.316-5C>T Uncertain significance ★ 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/hbd-p-lys121 (accessed [today's date]).

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