Is EEIG1 p.Pro196Arg (c.587C>G) pathogenic?

EEIG1 p.Pro196Arg (c.587C>G) is classified Uncertain significance in EEIG1 (ClinVar, Single submitter, 1 submitter; last evaluated 2023-06-07). AlphaMissense: likely benign (0.1044); Ultra-rare (popmax 0.0624%, eas).

How common is EEIG1 p.Pro196Arg (c.587C>G) in the general population?

EEIG1 p.Pro196Arg (c.587C>G) is ultra-rare (popmax 0.0624%, eas) (gnomAD).

What do computational predictors say about EEIG1 p.Pro196Arg (c.587C>G)?

AlphaMissense predicts likely benign (score 0.1044) — an in-silico prediction, not a clinical call.

EEIG1 p.Pro196Arg

c.587C>G · rs201955442 · VCV2510348

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.1044 · ACMG-weighted

gnomAD v4.1

Rare

ultra-rare (popmax 0.0624%, eas)

Missense predictors

0/3 damaging

AlphaMissense, REVEL, SaProt

Computational evidence

Protein change
AlphaMissense	0.1044	likely benign
REVEL	0.053	moderately benign-leaning
SaProt	LLR -7.01	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 2.8	GERP -3.2, phastCons 1
Regional constraint	o/e 0.87	unconstrained · MANE · 4,940 bp · p 0.025 · regional, not allelic
Overall
CADD	12.38	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 0.0624% East Asian · 28/44,876 alleles

Filtering AF 0.0443% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.0382%

Overall 0.0026% 42/1,612,788 alleles · ultra-rare exomes 39/1,460,470 · genomes 3/152,318 · joint denominator

Ancestry group	Frequency	1 in
East Asiangrpmax	0.0624%	1,603
South Asian	0.00659%	15,173
Remaining individualsnot grpmax-eligible	0.00641%	15,603
Admixed American	0.00167%	60,010
Finnishnot grpmax-eligible	0.00157%	63,696
European (non-Finnish)	0.00017%	589,943

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: EEIG1
Protein: p.Pro196Arg
Coding: c.587C>G
MANE Select: NM_001035254
dbSNP: rs201955442
Type: single nucleotide variant
Location: chr9:127948100 (GRCh38)
Structure: AlphaFold pLDDT 69.30
Residue 196: the 'disordered' region

Full EEIG1 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Similar variants

EEIG1 p.Pro196His Uncertain significance ★ ⚠ same residue
EEIG1 p.Ala326Val Uncertain significance ★ ⚠ same type
EEIG1 p.Arg118His Uncertain significance ★ ⚠ same type
EEIG1 p.Arg194Gln Uncertain significance ★ ⚠ same type
EEIG1 p.Arg228Gly Uncertain significance ★ ⚠ same type
EEIG1 p.Arg248Cys Uncertain significance ★ ⚠ same type
EEIG1 p.Arg258His Uncertain significance ★ ⚠ same type
EEIG1 p.Arg259Gly Uncertain significance ★ ⚠ 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/eeig1-p-pro196arg (accessed [today's date]).

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