Is IMPG2 p.Arg127Ter (c.379C>T) pathogenic?

IMPG2 p.Arg127Ter (c.379C>T) is classified Pathogenic in IMPG2 (ClinVar, Multiple submitters, 5 submitters; last evaluated 2024-02-21). Very rare (popmax 0.00195%, nfe); Associated with IMPG2-related disorders.

What condition is associated with IMPG2 p.Arg127Ter (c.379C>T)?

IMPG2 p.Arg127Ter (c.379C>T) is associated with IMPG2-related disorders (ClinVar).

How common is IMPG2 p.Arg127Ter (c.379C>T) in the general population?

IMPG2 p.Arg127Ter (c.379C>T) is very rare (popmax 0.00195%, nfe) (gnomAD).

IMPG2 p.Arg127Ter

c.379C>T · rs759184240 · VCV845633

Pathogenic Multiple submitters

Classification

Pathogenic

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 5 submitters

Consequence

nonsense (stop-gain)

predicted LoF

gnomAD v4.1

Rare

very rare (popmax 0.00195%, nfe)

Conditions

IMPG2-related disorders

Computational evidence

Protein change
Missense predictors do not apply to this variant type; conservation carries the signal.
Consequence	nonsense (stop-gain)	predicted loss-of-function
NMD	predicted	premature termination codon in exon 3 of 19
Splicing
SpliceAI	<0.2	all four deltas below 0.2 · G>T here scores Δ0.20 · evaluated, not missing
Constraint at this position
Conservation	phyloP 6.4	GERP 1.9, phastCons 1
Overall
CADD	37.0	PHRED · no single calibrated threshold — expert panels disagree

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

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.00195% European (non-Finnish) · 23/1,179,778 alleles

Filtering AF 0.0013% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.00108%

Overall 0.00149% 24/1,613,714 alleles · very rare exomes 22/1,461,618 · genomes 2/152,096 · joint denominator

Ancestry group	Frequency	1 in
European (non-Finnish)grpmax	0.00195%	51,295
South Asian	0.0011%	91,078

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.Arg127Ter
Coding: c.379C>T
MANE Select: NM_016247
dbSNP: rs759184240
Type: single nucleotide variant
Location: chr3:101304268 (GRCh38)
Gene constraint: LOEUF 0.773 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 54.28
Residue 127: a UniProt-annotated variant site (in rp56)

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

Disease context

IMPG2-related disorders

Similar variants

IMPG2 p.Arg127Pro Likely pathogenic ★ same residue
IMPG2 p.Arg127Gln Uncertain significance ★ ⚠ same residue
IMPG2 c.1240-1G>A Likely pathogenic ★★ same condition
IMPG2 c.1240-2A>G Pathogenic/Likely pathogenic ★★ same condition
IMPG2 c.502-2A>G Likely pathogenic ★★ same condition
IMPG2 c.667-1G>A Pathogenic/Likely pathogenic ★★ same condition
IMPG2 c.829-1G>T Pathogenic/Likely pathogenic ★★ same condition
IMPG2 p.Arg1088Ter Pathogenic/Likely pathogenic ★★ 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-arg127ter (accessed [today's date]).

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