Is HBD p.His98= (c.294C>T) pathogenic?

HBD p.His98= (c.294C>T) is classified Benign in HBD (ClinVar, Multiple submitters, 3 submitters; last evaluated 2019-12-31). Low-frequency (popmax 1.72%, afr).

How common is HBD p.His98= (c.294C>T) in the general population?

HBD p.His98= (c.294C>T) is low-frequency (popmax 1.72%, afr) (gnomAD).

HBD p.His98=

c.294C>T · rs61746501 · VCV708948

Benign Multiple submitters

Classification

Benign

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 3 submitters

gnomAD v4.1

Rare

low-frequency (popmax 1.72%, 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 -12	GERP -3.7
Overall
CADD	6.019	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 1.72% African / African-American · 1,293/75,000 alleles

Filtering AF 1.65% ClinGen BA1/BS1 input FAF95, joint · FAF99 1.61%

Overall 0.501% 8,083/1,613,984 alleles · low-frequency exomes 6,929/1,461,776 · genomes 1,154/152,208 · joint denominator

Ancestry group	Frequency	1 in
African / African-Americangrpmax	1.72%	58
Remaining individualsnot grpmax-eligible	0.552%	181
Middle Eastern	0.495%	202
European (non-Finnish)	0.49%	204
Admixed American	0.403%	248
Finnishnot grpmax-eligible	0.364%	275
South Asian	0.131%	765
Ashkenazi Jewishnot grpmax-eligible	0.108%	925
East Asian	0.0178%	5,610

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.His98=
Coding: c.294C>T
MANE Select: NM_000519
dbSNP: rs61746501
Type: single nucleotide variant
Location: chr11:5234012 (GRCh38)
Gene constraint: LOEUF 1.586 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 96.81 · 2 PDB
Residue 98: the globin domain

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

Similar variants

HBD p.Gly75= Uncertain significance ★★ same type
HBD p.Thr5Ile Uncertain significance ★★ ⚠ same type
HBD c.315+146T>G 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
HBD c.93-28G>C Uncertain significance ★ same type
HBD c.-118C>T Conflicting classifications of pathogenicity ★ 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-his98 (accessed [today's date]).

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