Is HBD p.Val2= (c.6G>A) pathogenic?

HBD p.Val2= (c.6G>A) is classified Uncertain significance in HBD (ClinVar, Single submitter, 1 submitter; last evaluated 2018-01-13). Ultra-rare (popmax 0.0602%, eas); Associated with Fetal hemoglobin quantitative trait locus 1.

What condition is associated with HBD p.Val2= (c.6G>A)?

HBD p.Val2= (c.6G>A) is associated with Fetal hemoglobin quantitative trait locus 1 (ClinVar).

How common is HBD p.Val2= (c.6G>A) in the general population?

HBD p.Val2= (c.6G>A) is ultra-rare (popmax 0.0602%, eas) (gnomAD).

HBD p.Val2=

c.6G>A · rs1454993638 · VCV879892

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

gnomAD v4.1

Rare

ultra-rare (popmax 0.0602%, eas)

Conditions

Fetal hemoglobin quantitative trait locus 1

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 -7.7	GERP -2
Overall
CADD	8.142	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.0602% East Asian · 27/44,870 alleles

Filtering AF 0.0424% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.0365%

Overall 0.00199% 29/1,459,226 alleles · ultra-rare

Ancestry group	Frequency	1 in
East Asiangrpmax	0.0602%	1,662
South Asian	0.0011%	91,048
European (non-Finnish)	8.49e-05%	1,177,626

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.Val2=
Coding: c.6G>A
MANE Select: NM_000519
dbSNP: rs1454993638
Type: single nucleotide variant
Location: chr11:5234428 (GRCh38)
Gene constraint: LOEUF 1.586 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 96.81 · 2 PDB
Residue 2: a modified residue (n-acetylalanine; in variant niigata); a UniProt-annotated variant site (in niigata)

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

Disease context

Fetal hemoglobin quantitative trait locus 1 — disease report on Sugi Atlas → Associated genes, phenotypes, clinical trials & treatments

Similar variants

HBD p.Gly75= Uncertain significance ★★ same condition
HBD c.*59C>G Uncertain significance ★ same condition
HBD c.*65T>C Uncertain significance ★ same condition
HBD c.*91G>A Uncertain significance ★ same condition
HBD c.*96G>T Uncertain significance ★ same condition
HBD p.Ala28Asp Uncertain significance ★ ⚠ same condition
HBD p.Ala28Ser Conflicting classifications of pathogenicity ★ ⚠ same condition
HBD p.Asn20= Uncertain significance ★ 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/hbd-p-val2 (accessed [today's date]).

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