Is HMBS p.Pro208fs (c.623del) pathogenic?

HMBS p.Pro208fs (c.623del) is classified Pathogenic in HMBS (ClinVar, Single submitter, 1 submitter; last evaluated 2021-12-11). No gnomAD frequency available for this variant.

How common is HMBS p.Pro208fs (c.623del) in the general population?

HMBS p.Pro208fs (c.623del) is no gnomAD frequency available for this variant (gnomAD).

HMBS p.Pro208fs

c.623del · rs2134876482 · VCV1458933

Pathogenic Single submitter

Classification

Pathogenic

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

Consequence

frameshift

predicted LoF

gnomAD v4.1

Not reported

no gnomAD frequency available for this variant

Computational evidence

Protein change
Missense predictors do not apply to this variant type; conservation carries the signal.
Consequence	frameshift	predicted loss-of-function in a haploinsufficient gene (ClinGen)
NMD	predicted	premature termination codon in exon 10 of 14
Splicing
SpliceAI	—	not assessed · substitutions only
Constraint at this position
Conservation	phyloP -0.001	GERP -4.6

Predicted loss-of-function is descriptive, not an applied PVS1 code.

Population frequency

dbSNP / gnomAD

No gnomAD frequency available for this variant. This is missing data, not an absence: the variant may or may not be present in gnomAD. Rarity (ACMG PM2) and BA1/BS1 cannot be assessed for it.

Variant & gene context

Gene: HMBS
Protein: p.Pro208fs
Coding: c.623del
MANE Select: NM_000190
dbSNP: rs2134876482
Type: Deletion
Location: chr11:119092133 (GRCh38)
Gene constraint: LOEUF 0.546 · pLI 0.81 · ClinGen HI 3/3 (gnomAD)
Structure: AlphaFold pLDDT 90.54 · 11 PDB
Residue 208: a turn

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

Similar variants

HMBS p.Pro208= Likely benign ★ same residue
HMBS p.Asp289fs Pathogenic/Likely pathogenic ★★ same type
HMBS p.Lys272fs Likely pathogenic ★★ same type
HMBS c.160_160+1del Pathogenic ★ same type
HMBS c.605_612+7del Likely pathogenic ★ same type
HMBS c.651+244del Pathogenic ★ same type
HMBS c.652-2del Pathogenic ★ same type
HMBS c.87+2_87+4del Likely 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/hmbs-p-pro208fs (accessed [today's date]).

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