Is HBB p.Val134= (c.402G>C) pathogenic?

HBB p.Val134= (c.402G>C) is classified Conflicting classifications of pathogenicity in HBB (ClinVar, Conflicting submitters, 10 submitters; last evaluated 2026-04-01). Rare (popmax 0.534%, nfe); Associated with Inborn genetic diseases.

What condition is associated with HBB p.Val134= (c.402G>C)?

HBB p.Val134= (c.402G>C) is associated with Inborn genetic diseases, sickle cell disease, beta thalassemia (ClinVar).

How common is HBB p.Val134= (c.402G>C) in the general population?

HBB p.Val134= (c.402G>C) is rare (popmax 0.534%, nfe) (gnomAD).

HBB p.Val134=

c.402G>C · rs113082294 · VCV36327

Conflicting classifications of pathogenicity Conflicting submitters

Classification

Conflicting classifications of pathogenicity

ClinVar

Review

Conflicting submitters ★☆☆☆

ClinVar · 10 submitters

gnomAD v4.1

Rare

rare (popmax 0.534%, nfe)

Conditions

Inborn genetic diseases

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 -0.027	GERP 1, phastCons 0.001
Overall
CADD	8.165	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.534% European (non-Finnish) · 6,306/1,179,938 alleles

Filtering AF 0.523% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.519%

Overall 0.43% 6,934/1,614,048 alleles · rare exomes 6,465/1,461,790 · genomes 469/152,258 · joint denominator

Ancestry group	Frequency	1 in
European (non-Finnish)grpmax	0.534%	187
Remaining individualsnot grpmax-eligible	0.467%	214
Admixed American	0.34%	294
Amishnot grpmax-eligible	0.219%	456
Finnishnot grpmax-eligible	0.0906%	1,104
African / African-American	0.08%	1,250
Ashkenazi Jewishnot grpmax-eligible	0.0338%	2,960
East Asian	0.00223%	44,880
South Asian	0.0011%	91,078

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.Val134=
Coding: c.402G>C
MANE Select: NM_000518
dbSNP: rs113082294
Type: single nucleotide variant
Location: chr11:5225640 (GRCh38)
Gene constraint: LOEUF 1.964 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 97.09 · 350 PDB
Residue 134: a UniProt-annotated variant site (in extredemura); an α-helix; the globin domain

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

Disease context

Inborn genetic diseases — disease report on Sugi Atlas → Associated genes, phenotypes, clinical trials & treatments

Also linked: sickle cell disease beta thalassemia

Similar variants

HBB p.Val134Leu Uncertain significance ★★ same residue
HBB c.316-146T>G Pathogenic ★★★ same condition
HBB c.316-197C>T Pathogenic ★★★ same condition
HBB c.92+5G>C Pathogenic ★★★ same condition
HBB c.-78A>C Pathogenic ★★★ same condition
HBB c.*111A>G Pathogenic ★★★ same condition
HBB p.Ala28Ser Pathogenic ★★★ ⚠ same condition
HBB p.Lys18Ter Pathogenic ★★★ 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/hbb-p-val134 (accessed [today's date]).

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