Is IMPG2 p.Ile689= (c.2067C>T) pathogenic?

IMPG2 p.Ile689= (c.2067C>T) is classified Likely benign in IMPG2 (ClinVar, Single submitter, 1 submitter; last evaluated 2022-07-19). Very rare (popmax 0.00322%, nfe).

How common is IMPG2 p.Ile689= (c.2067C>T) in the general population?

IMPG2 p.Ile689= (c.2067C>T) is very rare (popmax 0.00322%, nfe) (gnomAD).

IMPG2 p.Ile689=

c.2067C>T · rs754267524 · VCV1142532

Likely benign Single submitter

Classification

Likely benign

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

gnomAD v4.1

Rare

very rare (popmax 0.00322%, nfe)

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 1.4	GERP -1.6, phastCons 0.98
Overall
CADD	0.44	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.00322% European (non-Finnish) · 38/1,180,010 alleles

Filtering AF 0.00239% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.0021%

Overall 0.00279% 45/1,613,928 alleles · very rare exomes 41/1,461,728 · genomes 4/152,200 · joint denominator

Ancestry group	Frequency	1 in
Finnishnot grpmax-eligible	0.00781%	12,798
European (non-Finnish)grpmax	0.00322%	31,053
Admixed American	0.00167%	59,986
Remaining individualsnot grpmax-eligible	0.0016%	62,476

Finnish shows a higher raw frequency than the grpmax group above it. gnomAD excludes bottlenecked groups — Finnish, Ashkenazi Jewish, Amish and “Remaining individuals” — from grpmax, because founder effects make their frequencies unrepresentative for filtering. The table is sorted by frequency, so an excluded group can sit above the grpmax row.

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: IMPG2
Protein: p.Ile689=
Coding: c.2067C>T
MANE Select: NM_016247
dbSNP: rs754267524
Type: single nucleotide variant
Location: chr3:101244264 (GRCh38)
Gene constraint: LOEUF 0.773 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 54.28
Residue 689: 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

Similar variants

IMPG2 p.Ile689fs Likely pathogenic ★ same residue
IMPG2 c.1240-1G>A Likely pathogenic ★★ same type
IMPG2 c.1240-2A>G Pathogenic/Likely pathogenic ★★ same type
IMPG2 c.502-2A>G Likely pathogenic ★★ same type
IMPG2 c.583+1G>C Pathogenic/Likely pathogenic ★★ same type
IMPG2 c.667-1G>A Pathogenic/Likely pathogenic ★★ same type
IMPG2 c.828+1G>A Pathogenic/Likely pathogenic ★★ same type
IMPG2 c.829-1G>T Pathogenic/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/impg2-p-ile689 (accessed [today's date]).

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