Is HBB p.Val2= (c.6G>T) pathogenic?

HBB p.Val2= (c.6G>T) is classified Likely benign in HBB (ClinVar, Single submitter, 1 submitter; last evaluated 2023-09-26). Very rare (popmax 0.000601%, nfe).

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

HBB p.Val2= (c.6G>T) is very rare (popmax 0.000601%, nfe) (gnomAD).

HBB p.Val2=

c.6G>T · rs1349384278 · VCV1612817

Likely benign Single submitter

Classification

Likely benign

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

gnomAD v4.1

Rare

very rare (popmax 0.000601%, nfe)

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 0.58	GERP 1, phastCons 1
Overall
CADD	7.225	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.000601% European (non-Finnish) · 7/1,164,618 alleles

Filtering AF 0.00025% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.000161%

Overall 0.000438% 7/1,597,322 alleles · very rare exomes 7/1,444,998 · genomes 0/152,324 · joint denominator

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.Val2=
Coding: c.6G>T
MANE Select: NM_000518
dbSNP: rs1349384278
Type: single nucleotide variant
Location: chr11:5227016 (GRCh38)
Gene constraint: LOEUF 1.964 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 97.09 · 350 PDB
Residue 2: a modified residue (n-acetylvaline); a modified residue (n-pyruvate 2-iminyl-valine; in hb a1b); a binding site; a UniProt-annotated variant site (in raleigh; o(2) affinity down)

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

Similar variants

HBB p.Val2Ala Conflicting classifications of pathogenicity ★ ⚠ same residue
HBB p.Val2Leu Uncertain significance ★ ⚠ same residue
HBB p.Val2Met Conflicting classifications of pathogenicity ★ ⚠ same residue
HBB p.Val2fs 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-val2 (accessed [today's date]).

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