Is IMPG2 p.Ser716Pro (c.2146T>C) pathogenic?

IMPG2 p.Ser716Pro (c.2146T>C) is classified Uncertain significance in IMPG2 (ClinVar, Multiple submitters, 2 submitters; last evaluated 2023-11-17). AlphaMissense: likely benign (0.0834); Ultra-rare (popmax 0.0156%, eas); Associated with Inborn genetic diseases.

What condition is associated with IMPG2 p.Ser716Pro (c.2146T>C)?

IMPG2 p.Ser716Pro (c.2146T>C) is associated with Inborn genetic diseases (ClinVar).

How common is IMPG2 p.Ser716Pro (c.2146T>C) in the general population?

IMPG2 p.Ser716Pro (c.2146T>C) is ultra-rare (popmax 0.0156%, eas) (gnomAD).

What do computational predictors say about IMPG2 p.Ser716Pro (c.2146T>C)?

AlphaMissense predicts likely benign (score 0.0834) — an in-silico prediction, not a clinical call.

IMPG2 p.Ser716Pro

c.2146T>C · rs779190337 · VCV1011395

Uncertain significance Multiple submitters

Classification

Uncertain significance

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 2 submitters

AlphaMissense

likely benign

0.0834 · ACMG-weighted

gnomAD v4.1

Rare

ultra-rare (popmax 0.0156%, eas)

Missense predictors

0/3 damaging

AlphaMissense, REVEL, SaProt

Conditions

Inborn genetic diseases

Computational evidence

Protein change
AlphaMissense	0.0834	likely benign
REVEL	0.169	moderately benign-leaning
SaProt	LLR -7.00	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 3.9	GERP 0.034, phastCons 1
Regional constraint	o/e 0.98	unconstrained · MANE · 93 kb · p 0.41 · regional, not allelic
Overall
CADD	17.32	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 0.0156% East Asian · 7/44,854 alleles

Filtering AF 0.00726% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.00515%

Overall 0.000434% 7/1,613,922 alleles · ultra-rare exomes 5/1,461,720 · genomes 2/152,202 · joint denominator

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.Ser716Pro
Coding: c.2146T>C
MANE Select: NM_016247
dbSNP: rs779190337
Type: single nucleotide variant
Location: chr3:101244185 (GRCh38)
Gene constraint: LOEUF 0.773 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 54.28
Residue 716: 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

Inborn genetic diseases — disease report on Sugi Atlas → Associated genes, phenotypes, clinical trials & treatments

Similar variants

IMPG2 p.Ala1230Ser Uncertain significance ★★ ⚠ same condition
IMPG2 p.Ala1231Val Uncertain significance ★★ ⚠ same condition
IMPG2 p.Ala207Thr Uncertain significance ★★ ⚠ same condition
IMPG2 p.Ala280Ser Uncertain significance ★★ ⚠ same condition
IMPG2 p.Ala419Asp Uncertain significance ★★ ⚠ same condition
IMPG2 p.Ala741Asp Uncertain significance ★★ ⚠ same condition
IMPG2 p.Ala978Thr Uncertain significance ★★ ⚠ same condition
IMPG2 p.Arg1048Gln 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-ser716pro (accessed [today's date]).

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