Is HBB p.Ala116Val (c.347C>T) pathogenic?

HBB p.Ala116Val (c.347C>T) is classified Uncertain significance in HBB (ClinVar, Single submitter, 1 submitter; last evaluated 2025-05-20). AlphaMissense: likely pathogenic (0.872); Absent from gnomAD v4.1.

How common is HBB p.Ala116Val (c.347C>T) in the general population?

HBB p.Ala116Val (c.347C>T) is absent from gnomAD v4.1 (gnomAD).

What do computational predictors say about HBB p.Ala116Val (c.347C>T)?

AlphaMissense predicts likely pathogenic (score 0.872) — an in-silico prediction, not a clinical call.

HBB p.Ala116Val

c.347C>T · VCV3902791

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely pathogenic

0.872 · ACMG-weighted

gnomAD v4.1

Absent

absent from gnomAD v4.1

Missense predictors

3/3 damaging

AlphaMissense, REVEL, SaProt

Computational evidence

Protein change
AlphaMissense	0.872	likely pathogenic
REVEL	0.793	moderately pathogenic-leaning
SaProt	LLR -12.97	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 3.6	GERP 1.9, phastCons 0.67
Regional constraint	o/e 0.88	unconstrained · MANE · 1,420 bp · p 0.11 · regional, not allelic
Overall
CADD	23.0	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.Ala116Val
Coding: c.347C>T
MANE Select: NM_000518
Type: single nucleotide variant
Location: chr11:5225695 (GRCh38)
Gene constraint: LOEUF 1.964 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 97.09 · 350 PDB
Residue 116: a UniProt-annotated variant site (in b-thal; hradec kralove; unstable); a UniProt-annotated variant site (in madrid; unstable); an α-helix; the globin domain

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

Similar variants

HBB p.Ala116Asp Pathogenic ★★ same residue
HBB p.Ala116Pro Pathogenic ★ same residue
HBB p.Ala116= Likely benign ★ same residue
HBB p.Ala116fs 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-ala116val (accessed [today's date]).

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