Is HBB p.Glu8Asp (c.24G>C) pathogenic?

HBB p.Glu8Asp (c.24G>C) is classified Uncertain significance in HBB (ClinVar, Single submitter, 1 submitter; last evaluated 2023-05-16). AlphaMissense: likely pathogenic (0.588); Absent from gnomAD v4.1.

How common is HBB p.Glu8Asp (c.24G>C) in the general population?

HBB p.Glu8Asp (c.24G>C) is absent from gnomAD v4.1 (gnomAD).

What do computational predictors say about HBB p.Glu8Asp (c.24G>C)?

AlphaMissense predicts likely pathogenic (score 0.588) — an in-silico prediction, not a clinical call.

HBB p.Glu8Asp

c.24G>C · rs138405215 · VCV2681985

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely pathogenic

0.588 · ACMG-weighted

gnomAD v4.1

Absent

absent from gnomAD v4.1

Missense predictors

3/3 damaging

AlphaMissense, REVEL, SaProt

Computational evidence

Protein change
AlphaMissense	0.588	likely pathogenic
REVEL	0.658	pathogenic-leaning
SaProt	LLR -11.93	damaging
⇒ AlphaMissense, REVEL and SaProt all call this damaging.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 2.1	GERP 1, phastCons 1
Regional constraint	o/e 0.88	unconstrained · MANE · 1,420 bp · p 0.11 · regional, not allelic
Overall
CADD	17.76	PHRED · no single calibrated threshold — expert panels disagree

ClinVar classifies this uncertain; the computational predictors unanimously lean damaging — a triage signal, not a reclassification

AlphaMissense carries the ACMG weight for missense; REVEL and SaProt are independent agreement signals.

Population frequency

gnomAD v4.1 · exomes + genomes

Absent from gnomAD v4.1. Not observed in any sequenced alleles — a rarity signal (ACMG PM2-supporting), not evidence of pathogenicity on its own.

Variant & gene context

Gene: HBB
Protein: p.Glu8Asp
Coding: c.24G>C
MANE Select: NM_000518
dbSNP: rs138405215
Type: single nucleotide variant
Location: chr11:5226998 (GRCh38)
Gene constraint: LOEUF 1.964 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 97.09 · 350 PDB
Residue 8: a functional site ((microbial infection) cleavage; by n.americanus apr-2); an α-helix; the globin domain; a UniProt-annotated variant site (in g-san jose; mildly unstable); a UniProt-annotated variant site (in g-siriraj)

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

Similar variants

HBB p.Glu8Ter Pathogenic ★★ same residue
HBB p.Glu8Lys Uncertain significance ★★ ⚠ same residue
HBB p.Glu8Gly Likely benign ★★ same residue
HBB p.Glu8= Conflicting classifications of pathogenicity ★ same residue
HBB p.Glu8del Likely pathogenic ★★ same residue
HBB p.Glu8delinsAspTer Pathogenic same residue
HBB c.316-146T>G Pathogenic ★★★ same type
HBB c.316-197C>T 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-glu8asp (accessed [today's date]).

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