Is IMPG2 p.Tyr287Cys (c.860A>G) pathogenic?

IMPG2 p.Tyr287Cys (c.860A>G) is classified Uncertain significance in IMPG2 (ClinVar, Multiple submitters, 2 submitters; last evaluated 2022-07-15). AlphaMissense: ambiguous (0.4922); Very rare (popmax 0.00223%, nfe).

How common is IMPG2 p.Tyr287Cys (c.860A>G) in the general population?

IMPG2 p.Tyr287Cys (c.860A>G) is very rare (popmax 0.00223%, nfe) (gnomAD).

What do computational predictors say about IMPG2 p.Tyr287Cys (c.860A>G)?

AlphaMissense predicts ambiguous (score 0.4922) — an in-silico prediction, not a clinical call.

IMPG2 p.Tyr287Cys

c.860A>G · rs1434734155 · VCV1007988

Uncertain significance Multiple submitters

Classification

Uncertain significance

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 2 submitters

AlphaMissense

ambiguous

0.4922 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 0.00223%, nfe)

Computational evidence

Protein change
AlphaMissense	0.4922	ambiguous
REVEL	0.373	indeterminate
SaProt	LLR -12.30	damaging
Splicing
SpliceAI	<0.2	no splice effect predicted · four deltas, not one · how we know
Constraint at this position
Conservation	phyloP 7.8	GERP 2.8, phastCons 1
Regional constraint	o/e 0.98	unconstrained · MANE · 93 kb · p 0.41 · regional, not allelic
Overall
CADD	25.8	PHRED · no single calibrated threshold — expert panels disagree

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

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.00223% European (non-Finnish) · 26/1,165,026 alleles

Filtering AF 0.00155% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.00132%

Overall 0.00175% 28/1,597,318 alleles · very rare exomes 26/1,445,094 · genomes 2/152,224 · joint denominator

Ancestry group	Frequency	1 in
European (non-Finnish)grpmax	0.00223%	44,809
Remaining individualsnot grpmax-eligible	0.00161%	61,940
African / African-American	0.00134%	74,586

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.Tyr287Cys
Coding: c.860A>G
MANE Select: NM_016247
dbSNP: rs1434734155
Type: single nucleotide variant
Location: chr3:101269542 (GRCh38)
Gene constraint: LOEUF 0.773 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 54.28
Residue 287: a UniProt-annotated variant site (in rp56); a UniProt-annotated variant site (in vmd5); the sea 1 domain

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

Similar variants

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
IMPG2 c.829-2A>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-tyr287cys (accessed [today's date]).

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