Is HMBS p.Asp240fs (c.716_717dup) pathogenic?

HMBS p.Asp240fs (c.716717dup) is classified Pathogenic in HMBS (ClinVar, Single submitter, 1 submitter; last evaluated 2023-02-08). No gnomAD frequency available for this variant.

How common is HMBS p.Asp240fs (c.716_717dup) in the general population?

HMBS p.Asp240fs (c.716_717dup) is no gnomAD frequency available for this variant (gnomAD).

HMBS p.Asp240fs

c.716_717dup · rs2497466564 · VCV2835560

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 11 of 14
Splicing
SpliceAI	—	not assessed · substitutions only
Constraint at this position
Conservation	phyloP 1.7	GERP -1.2, phastCons 1

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.Asp240fs
Coding: c.716_717dup
MANE Select: NM_000190
dbSNP: rs2497466564
Type: Duplication
Location: chr11:119092466 (GRCh38)
Gene constraint: LOEUF 0.546 · pLI 0.81 · ClinGen HI 3/3 (gnomAD)
Structure: AlphaFold pLDDT 90.54 · 11 PDB

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

Similar variants

HMBS p.Asp240Asn Uncertain significance ★★ ⚠ same residue
HMBS p.Asp240Gly Pathogenic ★ same residue
HMBS p.Asp240= Likely benign ★ same residue
HMBS p.Lys70Ter Pathogenic/Likely pathogenic ★★ same type
HMBS p.Asn118fs Pathogenic ★ same type
HMBS p.Asn322Ter Pathogenic ★ same type
HMBS p.Gln204fs Likely pathogenic ★ same type
HMBS p.Glu182fs 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-asp240fs (accessed [today's date]).

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