Is IMPG2 p.Arg68His (c.203G>A) pathogenic?

IMPG2 p.Arg68His (c.203G>A) is classified Uncertain significance in IMPG2 (ClinVar, Single submitter, 1 submitter; last evaluated 2025-01-15). AlphaMissense: likely benign (0.0631); Very rare (popmax 0.0011%, sas).

How common is IMPG2 p.Arg68His (c.203G>A) in the general population?

IMPG2 p.Arg68His (c.203G>A) is very rare (popmax 0.0011%, sas) (gnomAD).

What do computational predictors say about IMPG2 p.Arg68His (c.203G>A)?

AlphaMissense predicts likely benign (score 0.0631) — an in-silico prediction, not a clinical call.

IMPG2 p.Arg68His

c.203G>A · rs756723730 · VCV1439311

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.0631 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 0.0011%, sas)

Missense predictors

0/3 damaging

AlphaMissense, REVEL, SaProt

Computational evidence

Protein change
AlphaMissense	0.0631	likely benign
REVEL	0.007	strongly benign-leaning
SaProt	LLR -6.98	tolerated
⇒ AlphaMissense, REVEL and SaProt all call this tolerated.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP -1.3	GERP -3.5
Regional constraint	o/e 0.98	unconstrained · MANE · 93 kb · p 0.41 · regional, not allelic
Overall
CADD	0.7	PHRED · no single calibrated threshold — expert panels disagree

ClinVar classifies this uncertain; the computational predictors unanimously lean tolerated — a triage signal, not a reclassification

AlphaMissense carries the ACMG weight for missense; REVEL and SaProt are independent agreement signals.

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.0011% South Asian · 1/91,074 alleles

Overall 0.000124% 2/1,613,644 alleles · very rare exomes 2/1,461,422 · genomes 0/152,222 · joint denominator

Ancestry group	Frequency	1 in
South Asiangrpmax	0.0011%	91,074
European (non-Finnish)	8.48e-05%	1,179,818

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.Arg68His
Coding: c.203G>A
MANE Select: NM_016247
dbSNP: rs756723730
Type: single nucleotide variant
Location: chr3:101319715 (GRCh38)
Gene constraint: LOEUF 0.773 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 54.28

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

Similar variants

IMPG2 p.Arg68Cys Uncertain significance ★ ⚠ same residue
IMPG2 p.Arg68fs 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

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-arg68his (accessed [today's date]).

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