Is HBB p.Thr85= (c.255C>T) pathogenic?

HBB p.Thr85= (c.255C>T) is classified Likely benign in HBB (ClinVar, Single submitter, 1 submitter; last evaluated 2023-09-27). Very rare (popmax 0.00223%, eas).

How common is HBB p.Thr85= (c.255C>T) in the general population?

HBB p.Thr85= (c.255C>T) is very rare (popmax 0.00223%, eas) (gnomAD).

HBB p.Thr85=

c.255C>T · rs1334966870 · VCV1157531

Likely benign Single submitter

Classification

Likely benign

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

gnomAD v4.1

Rare

very rare (popmax 0.00223%, eas)

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 1.6	GERP 1.9, phastCons 1
Overall
CADD	7.89	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.00223% East Asian · 1/44,884 alleles

Filtering AF 0.000292% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.000211%

Overall 0.00062% 10/1,614,012 alleles · very rare exomes 9/1,461,858 · genomes 1/152,154 · joint denominator

Ancestry group	Frequency	1 in
East Asiangrpmax	0.00223%	44,884
African / African-American	0.00133%	74,922
European (non-Finnish)	0.000678%	147,502

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.Thr85=
Coding: c.255C>T
MANE Select: NM_000518
dbSNP: rs1334966870
Type: single nucleotide variant
Location: chr11:5226637 (GRCh38)
Gene constraint: LOEUF 1.964 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 97.09 · 350 PDB
Residue 85: a UniProt-annotated variant site (in kofu); a functional site ((microbial infection) cleavage; by n.americanus apr-2); an α-helix; the globin domain

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

Similar variants

HBB p.Thr85Ala Uncertain significance ★ ⚠ same residue
HBB p.Thr85Asn Uncertain significance ⚠ same residue
HBB p.Thr85fs Likely 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
HBB c.*111A>G 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-thr85 (accessed [today's date]).

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