Is IMPG2 p.Val553fs (c.1658del) pathogenic?

IMPG2 p.Val553fs (c.1658del) is classified Pathogenic in IMPG2 (ClinVar, Multiple submitters, 3 submitters; last evaluated 2025-11-19). No gnomAD frequency available for this variant; Associated with vitelliform macular dystrophy 5.

What condition is associated with IMPG2 p.Val553fs (c.1658del)?

IMPG2 p.Val553fs (c.1658del) is associated with vitelliform macular dystrophy 5 (ClinVar).

How common is IMPG2 p.Val553fs (c.1658del) in the general population?

IMPG2 p.Val553fs (c.1658del) is no gnomAD frequency available for this variant (gnomAD).

How is Adult-onset foveomacular vitelliform dystrophy inherited?

Typically Autosomal dominant, Not applicable (Orphanet). A genetic counselor can assess individual risk for a family.

IMPG2 p.Val553fs

c.1658del · rs1706456124 · VCV959814

Pathogenic Multiple submitters

Classification

Pathogenic

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 3 submitters

Consequence

frameshift

predicted LoF

gnomAD v4.1

Not reported

no gnomAD frequency available for this variant

Conditions

vitelliform macular dystrophy 5

Computational evidence

Protein change
Missense predictors do not apply to this variant type; conservation carries the signal.
Consequence	frameshift	predicted loss-of-function
NMD	predicted	premature termination codon in exon 13 of 19
Splicing
SpliceAI	—	not assessed · substitutions only
Constraint at this position
Conservation	phyloP -0.98	GERP -2.6

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: IMPG2
Protein: p.Val553fs
Coding: c.1658del
MANE Select: NM_016247
dbSNP: rs1706456124
Type: Deletion
Location: chr3:101244673 (GRCh38)
Gene constraint: LOEUF 0.773 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 54.28
Residue 553: a UniProt-annotated variant site (in rp56); a UniProt-annotated variant site (in vmd5)

Full IMPG2 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Disease context

vitelliform macular dystrophy 5 — disease report on Sugi Atlas → Associated genes, phenotypes, clinical trials & treatments

For Adult-onset foveomacular vitelliform dystrophy (Orphanet):

Inheritance: Autosomal dominant, Not applicable
Onset: Adult

Similar variants

IMPG2 p.Arg1088Ter Pathogenic/Likely pathogenic ★★ same condition
IMPG2 p.Arg906Ter Pathogenic ★★ same condition
IMPG2 p.Phe1016Ser Likely pathogenic ★★ same condition
IMPG2 p.Trp758Ter Pathogenic/Likely pathogenic ★★ same condition
IMPG2 p.Tyr171Ter Pathogenic/Likely pathogenic ★★ same condition
IMPG2 p.Ala686Thr Uncertain significance ★★ ⚠ same condition
IMPG2 p.Gly684Arg Uncertain significance ★★ ⚠ same condition
IMPG2 p.Leu842Met Uncertain significance ★★ ⚠ same condition

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/impg2-p-val553fs (accessed [today's date]).

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